Direct recruitment of polycomb repressive complex 1 to chromatin by core binding transcription factors.
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.
Children's Hospital Boston and Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Ming
M
Yu
Tali
T
Mazor
Hui
H
Huang
Hsuan-Ting
HT
Huang
Katie L
KL
Kathrein
Andrew J
AJ
Woo
Candace R
CR
Chouinard
Adam
A
Labadorf
Thomas E
TE
Akie
Tyler B
TB
Moran
Huafeng
H
Xie
Sima
S
Zacharek
Ichiro
I
Taniuchi
Robert G
RG
Roeder
Carla F
CF
Kim
Leonard I
LI
Zon
Ernest
E
Fraenkel
Alan B
AB
Cantor
D000818:Animals; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism*; D002846:Chromatography, Affinity; D016000:Cluster Analysis; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics / Q000378:metabolism*; D050658:Core Binding Factor beta Subunit / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006412:Hematopoietic Stem Cells / Q000502:physiology; D008533:Megakaryocytes / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D063150:Polycomb Repressive Complex 1; D063146:Polycomb-Group Proteins; D011485:Protein Binding; D055503:Protein Multimerization; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism; D060168:Thymocytes / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology / Q000235:genetics
C489421:Bmi1 protein, mouse; C493693:Cbfb protein, mouse; D002843:Chromatin; D050676:Core Binding Factor Alpha 2 Subunit; D050658:Core Binding Factor beta Subunit; D009687:Nuclear Proteins; D063146:Polycomb-Group Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; C493726:Runx1 protein, mouse; D063150:Polycomb Repressive Complex 1; C489842:Rnf2 protein, mouse; D044767:Ubiquitin-Protein Ligases