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MBC in Press, published online ahead of print November 15, 2006
Mol. Biol. Cell 10.1091/mbc.E06-06-0551

A more recent version of this article appeared on February 1, 2007
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Submitted on June 26, 2006
Revised on October 30, 2006
Accepted on November 3, 2006

NuMA Influences Higher Order Chromatin Organization in Human Mammary Epithelium

Patricia C. Abad,* Jason Lewis,* I. Saira Mian,{dagger} David Knowles,{dagger} Jennifer Sturgis,* Sunil Badve,{ddagger} Jun Xie,{sect} and Sophie A. Lelièvre*

*Department of Basic Medical Sciences and Cancer Center, Purdue University, West Lafayette, IN 47907-2026; {dagger}Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720-8268; {ddagger}Indiana University School of Medicine, Indianapolis, IN 46202-5280; {sect}Department of Statistics, Purdue University, West Lafayette, IN 47907-2067

Monitoring Editor: A. Gregory Matera

The coiled-coil protein NuMA is an important contributor to mitotic spindle formation and stabilization. A potential role for NuMA in nuclear organization or gene regulation is suggested by the observations that its pattern of nuclear distribution depends upon cell phenotype and that it interacts and/or colocalizes with transcription factors. To date, the precise contribution of NuMA to nuclear function remains unclear. Previously, we observed that antibody-induced alteration of NuMA distribution in growth-arrested and differentiated mammary epithelial structures (acini) in three-dimensional culture triggers the loss of acinar differentiation. Here, we show that in mammary epithelial cells, NuMA is present in both the nuclear matrix and chromatin compartments. Expression of a portion of the C-terminus of NuMA that shares sequence similarity with the chromatin regulator HPC2 is sufficient to inhibit acinar differentiation, and results in the redistribution of NuMA, chromatin markers acetyl-H4 and H4K20m, and regions of DNase I-sensitive chromatin compared with control cells. Short-term alteration of NuMA distribution with anti-NuMA C-terminus antibodies in live acinar cells indicates that changes in NuMA and chromatin organization precede loss of acinar differentiation. These findings suggest that NuMA has a role in mammary epithelial differentiation by influencing the organization of chromatin.

Address correspondence to: Sophie A. Lelièvre (lelievre{at}purdue.edu)




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