NuMA influences higher order chromatin organization in human mammary epithelium

Patricia C. Abad, Jason Lewis, I. Saira Mian, David W. Knowles, Jennifer Sturgis, Sunil Badve, Jun Xie, Sophie A. Lelièvre

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

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 deoxyribonuclease 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.

Original languageEnglish (US)
Pages (from-to)348-361
Number of pages14
JournalMolecular Biology of the Cell
Volume18
Issue number2
DOIs
StatePublished - Feb 2007

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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