Journal
MOLECULAR ONCOLOGY
Volume 9, Issue 1, Pages 218-235Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.molonc.2014.08.007
Keywords
MTA1; Chromatin; Histone H1; in-vivo; Nucleosome remodeling and histone deacetylation complex (NuRD)
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Funding
- National 973 Project [2009CB521807, 2015CB553904]
- National Natural Science Foundation of China [81071773, 81372158, 81372159, 81101518]
- Basic Scientific Research Funds from Peking Union Medical College [JK2010B27, 2012JKB13]
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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. (C) 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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