MTA1 regulates higher-order chromatin structure and histone H1-chromatin interaction in-vivo

Mol Oncol. 2015 Jan;9(1):218-35. doi: 10.1016/j.molonc.2014.08.007. Epub 2014 Aug 27.

Abstract

In the current study, for the first time, we found that metastasis-associated gene 1 (MTA1) was a higher-order chromatin structure organizer that decondenses the interphase chromatin and mitotic chromosomes. MTA1 interacts dynamically with nucleosomes during the cell cycle progression, prominently contributing to the mitotic chromatin/chromosome structure transitions at both prophase and telophase. We showed that the decondensation of interphase chromatin by MTA1 was independent of Mi-2 chromatin remodeling activity. H1 was reported to stabilize the compact higher-order chromatin structure through its interaction with DNA. Our data showed that MTA1 caused a reduced H1-chromatin interaction in-vivo. Moreover, the dynamic MTA1-chromatin interaction in the cell cycle contributed to the periodical H1-chromatin interaction, which in turn modulated chromatin/chromosome transitions. Although MTA1 drove a global decondensation of chromatin structure, it changed the expression of only a small proportion of genes. After MTA1 overexpression, the up-regulated genes were distributed in clusters along with down-regulated genes on chromosomes at parallel frequencies.

Keywords: Chromatin; Histone H1; MTA1; Nucleosome remodeling and histone deacetylation complex (NuRD); in-vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromatin Assembly and Disassembly / physiology*
  • Down-Regulation / physiology
  • HEK293 Cells
  • Histone Deacetylases / genetics
  • Histone Deacetylases / metabolism*
  • Histones / genetics
  • Histones / metabolism*
  • Humans
  • Nucleosomes / genetics
  • Nucleosomes / metabolism*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Trans-Activators
  • Up-Regulation / physiology

Substances

  • Histones
  • MTA1 protein, human
  • Nucleosomes
  • Repressor Proteins
  • Trans-Activators
  • Histone Deacetylases