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Vol. 19, Issue 1, 1-7, January 2008
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Essay
Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892
Monitoring Editor: Gerard Evan
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ABSTRACT |
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In a recent review, A. Groth and coworkers presented a comprehensive account of nucleosome disassembly in front of a DNA replication fork, assembly behind the replication fork, and the copying of epigenetic information onto the replicated chromatin. Understanding those processes however would be enhanced by a comprehensive graphical depiction analogous to a circuit diagram. Accordingly, we have constructed a molecular interaction map (MIM) that preserves in essentially complete detail the processes described by Groth et al. The MIM organizes and elucidates the information presented by Groth et al. on the complexities of chromatin replication, thereby providing a tool for system-level comprehension of the effects of genetic mutations, altered gene expression, and pharmacologic intervention.
Bioregulatory systems often are composed of a network of molecular interactions that is so complex as to challenge comprehensive description in linear text. A graphical description akin to a circuit diagram can then be of great value. In the current work, we assembled a molecular interaction map (MIM; Kohn, 1999
, 2006a,b) based on information from an excellent recent review of molecular events during chromatin replication (Groth et al., 2007), and we discuss how the MIM provides a fresh integrated and detailed (albeit incomplete) view of the system. In addition, we point out some to the areas that remain to be covered to complete the picture.
During DNA replication, nucleosomes are disassembled ahead of the replication fork and reassembled, together with newly synthesized histones, on the daughter DNA strands. At the same time, the epigenetic information that is encoded as chromatin modifications is copied from the parental chromatin onto the daughter chromatin strands. These chromatin modifications (such as DNA methylation, histone methylation, and histone acetylation) are part of the complex system that influences gene expression patterns and cell differentiation state. Replication provides an opportunity for chromatin modifications to be copied faithfully or to be altered as cells change their differentiation state.
In their recent review, Groth et al. (2007) discussed the molecular events that bring about disassembly of nucleosomes ahead of the replication fork, assembly of nucleosomes on the daughter DNA strands, and copying of chromatin modifications. They described those events in a clear and detailed manner, thereby enabling us to assemble the relevant information in the form of a molecular interaction map (Kohn et al., 2006a,b) that shows graphically how chromatin replication operates and how chromatin modification state is preserved. The MIM retains and integrates essentially all of the molecular details presented in their review, thus providing the equivalent of a circuit diagram in electronics. The MIM provides an essential tool for troubleshooting the effects of genetic mutations, altered gene expression, or specific inhibitory drugs.
It is important to recognize that the picture presented here is confined to the molecular interactions discussed by Groth et al. and is necessarily incomplete. A more complete picture of how epigenetic information is preserved during replication would have to consider the copying from parental to daughter chromatin of other histone modifications, such as phosphorylation, ubiquitinylation, glycosylation, sumoylation, and ADP-ribosylation, as well as the copying of histone variant patterns.
Figure 1 defines the symbols used in the MIM (Figure 2). Appendix 1 summarizes the relevant MIM notation rules. Appendix 2 explains each interaction shown in the MIM and provides other relevant information, as well as references cited by Groth et al. To help the reader find any molecular species or interaction on the MIM, Appendix 3 provides a Location Table giving coordinates in the manner of a roadmap. We have also prepared an electronic version (eMIM) in which the annotations and locations can be navigated automatically and links to other databases are provided (http://discover.nci.nih.gov/mim/index.jsp).
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DISASSEMBLY OF PRE-EXISTING NUCLEOSOMES |
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FACT binds and removes H2A:H2B dimers from nucleosomes [6], leading to nucleosome disruption. H2A:H2B dimers can exchange continually, whereas the nucleosomal core histones, H3:H4, are more stable (Kimura and Cook, 2001). As long as H2A:H2B dimers remain bound to (H3:H4)2 tetramers on DNA [5], the nucleosome remains intact; when FACT removes the H2A:H2B dimers, the nucleosome is destabilized, and H3:H4 as dimers or tetramers can translocate to nucleosomes assembling behind the replication fork.
The FACT-bound H2A:H2B dimers [6] provide a pool of H2A:H2B for later use in assembly of nucleosomes behind the replication fork (details of the H3:H4 translocation mechanism are unknown).
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ASSEMBLY OF NEW NUCLEOSOMES |
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). H3:H4 dimers from disassembled nucleosomes may transfer randomly to the leading and lagging DNA strands and then combine with newly synthesized H3:H4 dimers [11] to form new tetramers. This is an attractive mechanism whereby the histone modification state could be copied from the old to the newly synthesized H3:H4 dimers (Groth et al., 2007), analogous to the way DNA methylation is copied from pre-existing DNA to daughter DNA (see below). (For simplicity, the MIM show H3:H4 binding to the leading strand only.) To complete the assembly of new nucleosomes, two H2A:H2B dimers then add to the (H3:H4)2 tetramers [12, 13]. The MIM suggests that FACT binds H2A:H2B (pre-existing and/or newly synthesized) [6] in competition with (H3:H4)2 tetramers; consequently, there may be a pool of FACT-bound H2A:H2B that would make H2A:H2B dimers available wherever (H3:H4)2 tetramers may occur. To see this situation in more detail, note that there are three branches in the binding line that connects H2A:H2B dimers with (H3:H4)2 tetramers: 1) binding to a pre-existing (H3:H4)2 tetramer ahead of the replication fork (this branch normally tends to go in the direction of dissociation) [5]; 2) binding to a pre-existing tetramer behind the fork (on a semiconservatively replicated DNA strand) [12]; and 3) binding to a tetramer consisting of a pre-existing H3:H4 dimer and a newly synthesized H3:H4 dimer [13]. The MIM suggests that FACT could, in principle, facilitate H2A:H2B transfer in either direction across the replication fork. Normally, the accumulation of newly replicated DNA would pull the transfer from ahead of the fork to behind it. When a replication fork has stalled, however, histone transfers may go in either direction, with potentially long-term effects on the local histone modification state (see below).
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COPYING THE DNA METHYLATION STATE ONTO NEWLY SYNTHESIZED DNA |
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The DNA methyltransferase DNMT1 has multiple binding capabilities that allow it to play a central role in this process. Its DNA methyltransferase function is accomplished through binding to hemimethylated CpG sites, whereupon the enzyme methylates the cytosine on the complementary (newly replicated) DNA strand [27, 28]. (The enzyme reaction symbol [27] implies the existence of an intermediate in which enzyme is bound to substrate.) The efficiency of this process is enhanced by the binding of DNMT1 to PCNA [29]. The binding to PCNA places the enzyme behind the replication fork near sites of DNA synthesis [20], where a pre-existing methylated DNA strand would be paired with a newly synthesized unmethylated strand. This arrangement allows DNA methylation pattern to be copied at the precise time and place of DNA replication. We shall see that an analogous arrangement allows the histone modification pattern to be copied.
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COPYING HISTONE MODIFICATIONS DURING THE ASSEMBLY OF REPLICATED CHROMATIN |
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The two methylases that bind to DNMT1 act on different H3 sites: G9a methylates lysine-9 [32], and EZH2 methylates lysine-27 [33], thereby perhaps coordinating the methylation of the two sites. The remaining two methylases (SETDB1 and Suv39h) also act on H3 lysine-9, making three different methylases that act on the same site. The reason for this duplication is unclear; perhaps their actions are invoked in structurally different types of chromatin (e.g., G9a in euchromatin, SETDB1 in euchromatin or heterochromatin, and Suv39h in heterochromatin).
Although there is no clear evidence of the role of HDACs binding to PCNA, it is tempting to speculate that it is dedicated to deacetylation of histones incorporated into nucleosomes formed behind the replication fork.
Methylase HP1 binds stably to lysine-9 sites on histone H3 [38a], suggesting the possibility that HP1 is recruited to such sites on pre-existing H3, putting it in position to act on newly synthesized H3 on the same newly formed nucleosome. The interlocked binding network may localize other components of the methylation system through HP1 to those newly formed nucleosomes that require H3 methylation.
The system of interlocked components of the chromatin modification system can link also to hemi-methylated CpG sites on DNA, mediated via MBD1 [34] and possibly also via DNMT1 (if this enzyme binds stably to its substrate). The interlocked system of chromatin modification molecules, as already mentioned, could be envisioned as a molecular cluster localized to replication sites through binding to PCNA. (Such a cluster however could not be mediated by a single PCNA trimer alone, because the trimer probably has only three binding sites.) When new nucleosomes bearing a methylated H3 appear, all of the players may become bound together at the site of newly synthesized/assembled chromatin, allowing prompt, efficient, and coordinated copying of the epigenetic information.
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CONTROL OF REPLICATION TIMING |
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or http://discover.nci.nih.gov). Hsk1/Cdc7 phosphorylates the p150 subunit of CAF-1 [22], an evolutionarily conserved three-subunit protein that exists in complex with newly synthesized H3.1:H4 dimers and deposits them in the construction of newly replicated chromatin. (CAF-1 does not associate with H3.3, whose incorporation into chromatin is independent of DNA replication and which is considered to be a replacement histone, as opposed to the major histone H3.1; Groth et al., 2007). CAF-1 functions in concert with Asf-1, which can bind to H3:H4 dimers directly [25]. A complex containing Asf-1, CAF-1, and newly synthesized H3:H4 may localize to replication sites behind the replication fork by way of direct binding between CAF-1 and PCNA [19]. The binding of the complex to PCNA however is potentially blocked by the ability of CAF-1 to form a homodimer [23]. Phosphorylation of the p150 subunit by Cdc7:Dfb4 [22] stabilizes p150 in a monomeric conformation and allows p150 binding to PCNA. This scenario is supported by the findings that 1) H3:H4 binding to CAF-1 and deposition onto chromatin are promptly blocked by inhibitors of DNA replication and 2) newly synthesized H3:H4 may not lead to the direct formation of tetramer (references cited by Groth et al., 2007). The mechanism described here may be how the timing of deposition of newly synthesized H3:H4 on DNA is coordinated with the timing of DNA replication. Because histone modifying enzymes (methylases, HATs, and HDACs) are also recruited to chromatin via PCNA, histone modifications concomitant with the deposition of new nucleosomes ensure the perpetuation of epigenetic marks on newly synthesized chromatin. |
LINKS TO OTHER MIMs |
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PCNA recruits many proteins to sites of DNA replication. Figure 2 shows only those involved in nucleosome formation and chromatin modification. The abbreviated PCNA box [48] however links to a MIM that shows the association of PCNA with other proteins involved in DNA replication, DNA repair, and cell cycle control (http://discover.nci.nih.gov/mim/kohnk/fig6b.html; Kohn, 1999). Links to other MIMs can be accessed at http://discover.nci.nih.gov/mim/index.jsp.
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WHAT DO WE GAIN FROM THE MIM? |
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The value of this systematic MIM representation is illustrated by its depiction of the role of PCNA. It has been noted that PCNA may be a hub for the assembly, close behind the replication fork, of a set of proteins that function in chromatin replication and modification (Groth et al., 2007). The MIM for the first time displays the intricacies of that assembly, showing how each component relates to the others. Examination of the MIM suggests which of those proteins can assemble, with or without PCNA, at DNA sites of CpG methylation and/or sites of histone H3 lysine-9 methylation. The interactions that may be required to coordinate particular chromatin replication functions also can be read from the MIM. Another interesting possibility suggested by the MIM was that CAF-1 might promote dissociation and stabilization H2A:H2B dimers from nucleosomes on either side of the replication fork, thereby perhaps allowing nucleosome transfer in reverse at stalled replication forks with consequent loss of epigenetic information.
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APPENDIX 1 |
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. A complete description with examples is provided in Kohn et al. (2006b). 1. A named molecular species usually appears in only one place on a map.
2. Interactions between molecular species are shown by different types of connecting lines (Figure 1).
3. Interaction lines can change direction, but not by more than 90° at a corner; this restriction prevents ambiguities at branch points.
4. When lines cross, it is as if they do not touch.
5. Color is optional and does not affect symbol definitions. We use red for inhibitions and other negative actions, green for stimulatory or catalytic actions, blue for covalent modifications, and purple for replication, transcription, and translation.
6. A small filled circle ("node") on an interaction line indicates the consequence or product of the interaction. Thus the consequence of binding between two molecules is formation of a dimer, which is represented by a node on the binding interaction line. The consequence of a modification (e.g., phosphorylation) is production of the modified (e.g., phosphorylated) molecule; the phosphorylated product is represented by a node placed on the modification line.
7. Multiple nodes on an interaction line represent exactly the same molecular species. A node should not be placed at a line crossing or at a corner where a line changes direction.
8. An isolated node (a node that is not on a line) is an abbreviation that represents another copy of the same molecular species that is defined at the other end of the line pointing to the node (to avoid ambiguity, only one arrow should point to an isolated node).
9. Molecular interactions are of two types: reactions and contingencies, as listed in Figure 1. Reactions operate on molecular species; contingencies operate on reactions or on other contingencies.
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APPENDIX 2 |
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. [1–5] The nucleosome core particle consists of two H3:H4 dimers [1] bound together to form an (H3:H4)2 tetramer [2] that is bound to DNA [3]. Two H2A:H2B dimers [4] bind individually to each H3:H4 dimer in a DNA-bound (H3:H4)2 tetramer, thus forming a complete nucleosome. Interaction [5] shows the binding of H2A:H2B dimers to DNA-bound (H3:H4)2 tetramers; the boxed "2" on the interaction line indicates that two H2A:H2B dimers bind per (H3:H4)2 tetramer.
[6] FACT ("facilitates chromatin transcription") binds H2A:H2B dimers, thereby dislodging them from the nucleosomes. Because FACT is bound via MCM ahead of the replication fork (see interactions [13, 14] below), the presumption is that FACT here is acting on pre-existing nucleosomes ahead of the replication fork.
[8–11] The remaining (H3:H4)2 tetramers [2] may be transferred intact, retaining their posttranscriptional modifications and may bind randomly to either daughter DNA strand [8] behind the replication fork. (The mechanism of transfer of H3:H4 is unknown.) Recent evidence however suggests that newly synthesized H3:H4 [9] are deposited onto newly synthesized DNA as dimers, not tetramers (Polo and Almouzni, 2006). H3:H4 dimers from dissociated nucleosomes may be transferred randomly to the daughter strands [10] and may then become associated with newly synthesized H3:H4 dimers [11] from a chaperone-bound pool ([17], described below); this mechanism would help explain how posttranscriptional information is copied to newly synthesized core histones (Groth et al., 2007).
[12, 13] Two H2A:H2B dimers (possibly released from FACT binding) then add to the (H3:H4)2 tetramers on daughter strand, whether the tetramers were transferred intact [12] or assembled from a pre-existing and a newly synthesized H3:H4 dimer [13]. (FACT also mediates H2A:H2B dimer transfer during transcription, thereby facilitating RNA polymerase progression [Belotserkovskaya and Reinberg, 2004].)
[14–16] FACT binds to the MCM helicase complex [14] (Gambus et al., 2006; Tan et al., 2006). MCM binds and unwinds DNA ahead of DNA polymerase during replication [15, 16] (Takahashi et al., 2005). (The arrow marked "H" represents the helix unwinding process.) Thus FACT may coordinate H2A:H2B histone transfer and DNA unwinding during replication.
[17–18] CAF-1 (chromatin-assembly factor, an evolutionarily conserved 3-subunit protein) binds to a complex of newly synthesized H3:H4 and Asf-1 ([17] and see [25a] below). The newly synthesized H3:H4 dimers can then be deposited from this chaperone complex onto newly synthesized DNA [11, 18]. A newly synthesized H3:H4 dimer may be first to bind newly synthesized DNA, then being joined by a transferred H3:H4 dimer (not shown), or these bindings may occur in the reverse order (as indicated in the MIM: [10] followed by [11]). The predeposition complex specifically contains H3.1:H4 (Tagami et al., 2004). Hydroxyurea blocks replication fork progression and consequently may prevent CAF-1–dependent histone deposition. Asf1 can then buffer the excess cytosolic newly synthesized H3:H4. (The order of binding of CAF-1 and Asf1 to newly synthesized H3:H4 shown in the MIM is hypothetical.)
[19–21] CAF-1 binds to PCNA [19] and is thereby directed to sites of DNA replication [20, 21] (Taddei et al., 1999; Sporbert et al., 2002). (The arrow marked "P" represents replication by DNA polymerase on the leading strand; replication on the lagging strand is not shown.) CAF1:PCNA remains bound to newly synthesized DNA for 20 min (corresponding to the replication of 20–40 kb of DNA), thereby providing a "window of opportunity" for modification of newly synthesized chromatin (Groth et al., 2007).
[22] Binding of CAF-1 to PCNA depends on phosphorylation of the CAF-1 large subunit (human p150), catalyzed by the essential kinase Hsk1/Cdc7:Dpf1/Dbf4 (Gerard et al., 2006). This kinase is enclosed in a dashed green box to indicate that its interactions are shown in more detail in another MIM (Aladjem et al., 2004; see eMIM).
[23–24] CAF-1 p150 contains a dimerization domain [23] (Moggs et al., 2000; Gerard et al., 2006). Dimerization competes with PCNA for binding to CAF-1 monomer [19]. The Cdc:Dbf4-catalyzed phosphorylation of CAF-1 p150 inhibits the dimerization [24] (i.e., stabilizes p150 in a monomer configuration) and thereby enhances the binding of CAF-1 p150 monomer to PCNA (Gerard et al., 2006).
[25a–c] Asf1 ("anti-silencing function 1") is a highly conserve chaperone that binds soluble H3:H4 [25a]. Asf1 may work together with CAF-1 to assemble nucleosomes during replication (Tyler et al., 1999; Mello et al., 2002; Groth et al., 2005). Asf1 binding to H3:H4 dimer prevents the dimers from coming together to form tetramers [25b and c] (English et al., 2005, 2006; Mousson et al., 2005). One might anticipate (hypothetically) that, in the absence Asf1, newly synthesized unmodified (H3:H4)2 tetramers could add onto newly replicated DNA and cause loss of histone modification information.
[26] H3.3 is not associated with CAF-1, and is incorporated into chromatin as a "replacement histone" in a replication-independent manner (Groth et al., 2007).
[27–29] DNMT1, a maintenance DNA methyltransferase that acts on hemimethylated CpG sites to establish symmetrical C-methylations [27, 28], binds PCNA [29] and is thereby recruited to DNA replication forks (Leonhardt et al., 1992; Chuang et al., 1997). Although CAF-1 acts to maintain nucleosomal density throughout the replicated genome, DNMT1 acts primarily on epigenetically silenced DNA and functions to maintain the CpG and H3 methylations that confer silencing (Groth et al., 2007). Although DNMT1 is an essential methylase, the binding of DNMT1 to PCNA is not required for maintenance of DNA methylation in human cells (Spada et al., 2007).
[30–33] DNMT1 binds histone H3 methyltransferases G9a [30] and EZH2 [31], thereby perhaps recruiting them via PCNA to newly replicated DNA, where they could methylate H3 on newly formed chromatin. G9a methylates H3 at K9 [32] (Esteve et al., 2006), whereas EZH2 (a polycomb protein) methylates H3 at K27 [33] (Vire et al., 2006). These DNMT1–methyltransferase complexes may constitute binary memory modules that coordinate the maintenance of DNA and H3 methylations during replication of epigenetically silenced DNA (Esteve et al., 2006).
[34–37] MBD1 binds methylated CpG in DNA [34]; it also binds CAF1 [35] and SETDB1 [36], an H3K9 methyltransferase [37] (Sarraf and Stancheva, 2004). The CAF1:MBD1:SETDB1 complex maintains H3K9 methylation and stable silencing at certain genes in replicating cells (Groth et al., 2007). SETDB1 that is bound via MBD1 to methylated CpG in front of the replication fork may translocate to methylated CpG sites behind the replication fork, where SETDB1 would be in position to methylate newly deposited H3 (Sarraf and Stancheva, 2004).
[38–42] HP1 binds H3K9me3 in heterochromatin or at stably silenced genes [38a], where H3K9me3 marks gene repression (Maison and Almouzni, 2004; Feldman et al., 2006). HP1 binds CAF1 p150 directly [39] (Murzina et al., 1999). HP1 binds MBD1 [40](Fujita et al., 2003) and H3K9 methyltransferase Suv39h [41, 42] (Aagaard et al., 1999). Dnmt1 can bind HP1 directly [40a], thereby helping to maintain DNA methylation status at pericentric heterochromatin, as well as gene silencing (Fuks et al., 2000; Lehnertz et al., 2003; Esteve et al., 2006; Smallwood et al., 2007). MBD1 (via HP1) binds to a pre-existing methylated nucleosomal H3; Suv39h and SETDB1, in complex with MBD1 and/or HP1, could then methylate the corresponding site in a newly synthesized H3 molecule in the newly constituted nucleosome. These actions are said to be in trans (defined in Figure 1), indicated by the gapped stimulation symbols [38b and c].
[43–45] Histone deacetylases (HDAC) bind PCNA [43] and are thereby recruited to DNA replication sites [20] (Milutinovic et al., 2002), where they deacetylate lysines 4 and 12 of histone H4 [44]. HDAC may also bind to DNMT1 [45] (Fuks et al., 2000; Rountree et al., 2000).
[46] Newly synthesized H3:H4 dimers become acetylated at K5 and K12 of H4 (Loyola et al., 2006). These acetylations of H4 are introduced by the two-subunit acetyltransferase HAT1:RbAp46 and may be required for repair of stalled replication forks (Barman et al., 2006). The H4K5/K12 acetylations are removed 20–60 min after replication (Taddei et al., 1999).
[47] The MCM complex is a helicase that plays a critical role in DNA replication. A MIM showing the interactions of this complex can be viewed at http://discover.nci.nih.gov/mim/view.jsp?MIM = replication&selection = map&subMenu = replication.
[48] PCNA serves as a platform for other proteins involved in DNA repair and cell cycle checkpoint control. A MIM showing other interactions of PCNA can be viewed at http://discover.nci.nih.gov/mim/kohnk/fig6b.html (Kohn, 1999).
[49] Hsk1/Cdc7:Dpf1/Dbf4 is a kinase complex that phosphorylates CAF-1 p150 [22]. It also phosphorylates MCM proteins and other members of the replication pre-initiation complex (not shown). A MIM showing the interactions of this kinase can be viewed at http://discover.nci.nih.gov/mim/view.jsp?MIM= replication&selection=map&subMenu=replication.
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APPENDIX 3 |
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ACKNOWLEDGMENTS |
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Footnotes |
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1 References relating to each interaction shown in Figure 2 are cited in Appendix 2 and in the annotations associated with the eMIM at http://discover.nci.nih.gov/mim. 
2 The annotation references include those cited by Groth et al. (2007).
Address correspondence to: Kurt W. Kohn (kohnk{at}dc37a.nci.nih.gov)
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REFERENCES |
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Groth, A., Rocha, W., Verreault, A., and Almouzni, G. (2007). Chromatin challenges during DNA replication and repair. Cell 128, 721–733.[CrossRef][Medline]
Kohn, K. W. (1999). Molecular interaction map of the mammalian cell cycle control and DNA repair systems. Mol. Biol. Cell 10, 2703–2734.
Kohn, K. W., Aladjem, M. I., Kim, S., Weinstein, J. N., and Pommier, Y. (2006a). Depicting combinatorial complexity with the molecular interaction map notation. Mol. Syst. Biol 2, 4100088(Electronic).
Kohn, K. W., Aladjem, M. I., Weinstein, J. N., and Pommier, Y. (2006b). Molecular interaction maps of bioregulatory networks: a general rubric for systems biology. Mol. Biol. Cell 17, 1–13.
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ANNOTATION REFERENCES2 |
|---|
Barman, H. K., Takami, Y., Ono, T., Nishijima, H., Sanematsu, F., Shibahara, K., and Nakayama, T. (2006). Histone acetyltransferase 1 is dispensable for replication-coupled chromatin assembly but contributes to recover DNA damages created following replication blockage in vertebrate cells. Biochem. Biophys. Res. Commun 345, 1547–1557.[CrossRef][Medline]
Belotserkovskaya, R., and Reinberg, D. (2004). Facts about FACT and transcript elongation through chromatin. Curr. Opin. Genet. Dev 14, 139–146.[CrossRef][Medline]
Chuang, L. S., Ian, H. I., Koh, T. W., Ng, H. H., Xu, G., and Li, B. F. (1997). Human DNA-(cytosine-5) methyltransferase-PCNA complex as a target for p21WAF1. Science 277, 1996–2000.
English, C. M., Adkins, M. W., Carson, J. J., Churchill, M. E., and Tyler, J. K. (2006). Structural basis for the histone chaperone activity of asf1. Cell 127, 495–508.[CrossRef][Medline]
English, C. M., Maluf, N. K., Tripet, B., Churchill, M. E., and Tyler, J. K. (2005). ASF1 binds to a heterodimer of histones H3 and H4, a twostep mechanism for the assembly of the H3–H4 heterotetramer on DNA. Biochemistry 44, 13673–13682.[CrossRef][Medline]
Esteve, P. O., Chin, H. G., Smallwood, A., Feehery, G. R., Gangisetty, O., Karpf, A. R., Carey, M. F., and Pradhan, S. (2006). Direct interaction between DNMT1and G9a coordinates DNA and histone methylation during replication. Genes Dev 20, 3089–3103.
Feldman, N., Gerson, A., Fang, J., Li, E., Zhang, Y., Shinkai, Y., Cedar, H., and Bergman, Y. (2006). G9a-mediated irreversible epigenetic inactivation of Oct-3/4 during early embryogenesis. Nat. Cell Biol 8, 188–194.[CrossRef][Medline]
Fujita, N., Watanabe, S., Ichimura, T., Tsuruzoe, S., Shinkai, Y., Tachibana, M., Chiba, T., and Nakao, M. (2003). Methyl-CpG binding domain 1 (MBD1) interacts with the Suv39h1–HP1 heterochromatic complex for DNA methylation-based transcriptional repression. J. Biol. Chem 278, 24132–24138.
Fuks, F., Burgers, W. A., Brehm, A., Hughes-Davies, L., and Kouzarides, T. (2000). DNA methyltransferase Dnmt1 associates with histone deacetylase activity. Nat. Genet 24, 88–91.[CrossRef][Medline]
Fuks, F. et al. (2003). The DNA methyltransferases associate with HP1 and the SUV39H1 histone methyltransferase. Nucleic Acids Res 31, (9), 2305–2312.
Gambus, A., Jones, R. C., Sanchez-Diaz, A., Kanemaki, M., van Deursen, F., Edmondson, R. D., and Labib, K. (2006). GINS maintains association of Cdc45 with MCM in replisome progression complexes at eukaryotic DNA replication forks. Nat. Cell Biol 8, 358–366.[CrossRef][Medline]
Gerard, A., Koundrioukoff, S., Ramillon, V., Sergere, J. C., Mailand, N., Quivy, J. P., and Almouzni, G. (2006). The replication kinase Cdc7-Dbf4 promotes the interaction of the p150 subunit of chromatin assembly factor 1 with proliferating cell nuclear antigen. EMBO Rep 7, 817–823.[Medline]
Groth, A., Ray-Gallet, D., Quivy, J. P., Lukas, J., Bartek, J., and Almouzni, G. (2005). Human Asf1 regulates the flow of S phase histones during replicational stress. Mol. Cell 17, 301–311.[CrossRef][Medline]
Groth, A., Rocha, W., Verreault, A., and Almouzni, G. (2007). Chromatin challenges during DNA replication and repair. Cell 128, 721–733.[CrossRef][Medline]
Gruss, C., Wu, J., Koller, T., and Sogo, J. M. (1993). Disruption of the nucleosomes at the replication fork. EMBO J 12, 4533–4545.[Medline]
Jackson, V. (1988). Deposition of newly synthesized histones: hybrid nucleosomes are not tandemly arranged on daughter DNA strands. Biochemistry 27, 2109–2120.[CrossRef][Medline]
Kimura, H., and Cook, P. R. (2001). Kinetics of core histones in living human cells: little exchange of H3 and H4 and some rapid exchange of H2B. J. Cell Biol 153, 1341–1353.
Lehnertz, B. et al. (2003). Suv39h-mediated histone H3 lysine 9 methylation directs DNA methylation to major satellite repeats at pericentric heterochromatin. Curr. Biol 13, (14), 1192–1200.[CrossRef][Medline]
Leonhardt, H., Page, A. W., Weier, H. U., and Bestor, T. H. (1992). A targeting sequence directs DNA methyltransferase to sites of DNA replication in mammalian nuclei. Cell 71, 865–873.[CrossRef][Medline]
Loyola, A., Bonaldi, T., Roche, D., Imhof, A., and Almouzni, G. (2006). PTMs on H3 variants before chromatin assembly potentiate their final epigenetic state. Mol. Cell 24, 309–316.[CrossRef][Medline]
Maison, C., and Almouzni, G. (2004). HP1 and the dynamics of heterochromatin maintenance. Nat. Rev. Mol. Cell Biol 5, 296–304.[CrossRef][Medline]
Mello, J. A., Sillje, H. H., Roche, D. M., Kirschner, D. B., Nigg, E. A., and Almouzni, G. (2002). Human Asf1 and CAF-1 interact and synergize in a repair-coupled nucleosome assembly pathway. EMBO Rep 3, 329–334.[CrossRef][Medline]
Milutinovic, S., Zhuang, Q., and Szyf, M. (2002). Proliferating cell nuclear antigen associates with histone deacetylase activity, integrating DNA replication and chromatin modification. J. Biol. Chem 277, 20974–20978.
Moggs, J. G., Grandi, P., Quivy, J. P., Jonsson, Z. O., Hubscher, U., Becker, P. B., and Almouzni, G. (2000). A CAF-1-PCNA-mediated chromatin assembly pathway triggered by sensing DNA damage. Mol. Cell. Biol 20, 1206–1218.
Mousson, F. et al. (2005). Structural basis for the interaction of Asf1 with histone H3 and its functional implications. Proc. Natl. Acad. Sci. USA 102, 5975–5980.
Murzina, N., Verreault, A., Laue, E., and Stillman, B. (1999). Heterochromatin dynamics in mouse cells: interaction between chromatin assembly factor 1 and HP1 proteins. Mol. Cell 4, 529–540.[CrossRef][Medline]
Polo, S. E., and Almouzni, G. (2006). Chromatin assembly: a basic recipe with various flavours. Curr. Opin. Genet. Dev 16, 104–111.[CrossRef][Medline]
Rountree, M. R., Bachman, K. E., and Baylin, S. B. (2000). DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a complex at replication foci. Nat. Genet 25, 269–277.[CrossRef][Medline]
Sarraf, S. A., and Stancheva, I. (2004). Methyl-CpG binding protein MBD1 couples histone H3 methylation at lysine 9 by SETDB1 to DNA replication and chromatin assembly. Mol. Cell 15, 595–605.[CrossRef][Medline]
Smallwood, A., Estève, P. O., Pradhan, S., and Carey, M. (2007). Functional cooperation between HP1 and DNMT1 mediates gene silencing. Genes Dev 21, 1169–1178.
Sogo, J. M., Stahl, H., Koller, T., and Knippers, R. (1986). Structure of replicating simian virus 40 minichromosomes. The replication fork, core histone segregation and terminal structures. J. Mol. Biol 189, 189–204.[CrossRef][Medline]
Spada, F., Haemmer, A., Kuch, D, Rothbauer, U., Schermelleh, L., Kremmer, E., Carell, T., Längst, G., and Leonhardt, H. (2007). DNMT1 but not its interaction with the replication machinery is required for maintenance of DNA methylation in human cells. J. Cell Biol 176, 565–571.
Sporbert, A., Gahl, A., Ankerhold, R., Leonhardt, H., and Cardoso, M. C. (2002). DNA polymerase clamp shows little turnover at established replication sites but sequential de novo assembly at adjacent origin clusters. Mol. Cell 10, 1355–1365.[CrossRef][Medline]
Taddei, A., Roche, D., Sibarita, J. B., Turner, B. M., and Almouzni, G. (1999). Duplication and maintenance of heterochromatin domains. J. Cell Biol 147, 1153–1166.
Tagami, H., Ray-Gallet, D., Almouzni, G., and Nakatani, Y. (2004). Histone H3.1 and H3.3 complexes mediate nucleosome assembly pathways dependent or independent of DNA synthesis. Cell 116, 51–61.[CrossRef][Medline]
Takahashi, T. S., Wigley, D. B., and Walter, J. C. (2005). Pumps, paradoxes and ploughshares: mechanism of the MCM2–7 DNA helicase. Trends Biochem. Sci 30, 437–444.[CrossRef][Medline]
Tan, B. C., Chien, C. T., Hirose, S., and Lee, S. C. (2006). Functional cooperation between FACT and MCM helicase facilitates initiation of chromatin DNA replication. EMBO J 25, 3975–3985.[CrossRef][Medline]
Tyler, J. K., Adams, C. R., Chen, S. R., Kobayashi, R., Kamakaka, R. T., and Kadonaga, J. T. (1999). The RCAF complex mediates chromatin assembly during DNA replication and repair. Nature 402, 555–560.[CrossRef][Medline]
Vire, E. (2006). The Polycomb group protein EZH2 directly controls DNA methylation. Nature 439, 871–874.[CrossRef][Medline]
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ABSTRACT
DISASSEMBLY OF PRE-EXISTING...
