NuMA influences higher order chromatin organization in human mammary epithelium. Academic Article uri icon

Overview

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.

publication date

  • November 15, 2006

Research

keywords

  • Antigens, Nuclear
  • Cell Differentiation
  • Chromatin
  • Epithelial Cells
  • Mammary Glands, Human
  • Nuclear Matrix-Associated Proteins

Identity

PubMed Central ID

  • PMC1783787

Scopus Document Identifier

  • 33846795973

Digital Object Identifier (DOI)

  • 10.1091/mbc.e06-06-0551

PubMed ID

  • 17108325

Additional Document Info

volume

  • 18

issue

  • 2