Direct recruitment of polycomb repressive complex 1 to chromatin by core binding transcription factors.

TitleDirect recruitment of polycomb repressive complex 1 to chromatin by core binding transcription factors.
Publication TypeJournal Article
Year of Publication2012
AuthorsYu, M, Mazor, T, Huang, H, Huang, H-T, Kathrein, KL, Woo, AJ, Chouinard, CR, Labadorf, A, Akie, TE, Moran, TB, Xie, H, Zacharek, S, Taniuchi, I, Roeder, RG, Kim, CF, Zon, LI, Fraenkel, E, Cantor, AB
JournalMol Cell
Volume45
Issue3
Pagination330-43
Date Published2012 Feb 10
ISSN1097-4164
KeywordsAnimals, Cell Line, Chromatin, Chromatography, Affinity, Cluster Analysis, Core Binding Factor Alpha 2 Subunit, Core Binding Factor beta Subunit, Gene Expression Profiling, Gene Expression Regulation, Gene Knockdown Techniques, Hematopoietic Stem Cells, Megakaryocytes, Mice, Mice, Inbred C57BL, Mice, Knockout, Nuclear Proteins, Polycomb Repressive Complex 1, Polycomb-Group Proteins, Protein Binding, Protein Multimerization, Proto-Oncogene Proteins, Repressor Proteins, T-Lymphocytes, Thymocytes, Ubiquitin-Protein Ligases, Zebrafish
Abstract

Polycomb repressive complexes (PRCs) play key roles in developmental epigenetic regulation. Yet the mechanisms that target PRCs to specific loci in mammalian cells remain incompletely understood. In this study we show that Bmi1, a core component of Polycomb Repressive Complex 1 (PRC1), binds directly to the Runx1/CBFβ transcription factor complex. Genome-wide studies in megakaryocytic cells demonstrate significant chromatin occupancy overlap between the PRC1 core component Ring1b and Runx1/CBFβ and functional regulation of a considerable fraction of commonly bound genes. Bmi1/Ring1b and Runx1/CBFβ deficiencies generate partial phenocopies of one another in vivo. We also show that Ring1b occupies key Runx1 binding sites in primary murine thymocytes and that this occurs via PRC2-independent mechanisms. Genetic depletion of Runx1 results in reduced Ring1b binding at these sites in vivo. These findings provide evidence for site-specific PRC1 chromatin recruitment by core binding transcription factors in mammalian cells.

DOI10.1016/j.molcel.2011.11.032
Alternate JournalMol. Cell
PubMed ID22325351
PubMed Central IDPMC3278717
Grant ListP30 ES002109-31A1 / ES / NIEHS NIH HHS / United States
P30-ES002109 / ES / NIEHS NIH HHS / United States
R01 GM089903 / GM / NIGMS NIH HHS / United States
R01 GM089903-02 / GM / NIGMS NIH HHS / United States
R01 HL082952-04 / HL / NHLBI NIH HHS / United States
R01-GM089903 / GM / NIGMS NIH HHS / United States
R01-HL082952 / HL / NHLBI NIH HHS / United States
U54 CA112967-07 / CA / NCI NIH HHS / United States
U54-CA112967 / CA / NCI NIH HHS / United States