TY - JOUR
T1 - Role of Bmi-1 and Ring1A in H2A ubiquitylation and hox gene silencing
AU - Cao, Ru
AU - Tsukada, Yu Ichi
AU - Zhang, Yi
N1 - Funding Information:
We thank Maarten van Lohuizen for Bmi-1 null cells, Miguel Vidal for the Ring1A null cells and Ring1B antibodies, Robert Kingston for constructs, Eric Kallin for help in designing the PCR primers, and Cyrus Martin for critically reading the manuscript. Y.Z. is an Investigator of the Howard Hughes Medical Institute. This work was supported by the National Institutes of Health (GM68804) and the Howard Hughes Medical Institute.
PY - 2005/12/22
Y1 - 2005/12/22
N2 - Polycomb group (PcG) proteins exist in at least two biochemically distinct protein complexes, the EED-EZH2 complex and the PRC1 complex, that respectively possess H3-K27 methyltransferase and H2A-K119 ubiquitin E3 ligase activities. How the enzymatic activities are regulated and what their role is in Hox gene silencing are not clear. Here, we demonstrate that Bmi-1 and Ring1A, two components of the PRC1 complex, play important roles in H2A ubiquitylation and Hox gene silencing. We show that both proteins positively regulate H2A ubiquitylation. Chromatin immunoprecipitation (ChIP) assays demonstrate that Bmi-1 and other components of the two PcG complexes bind to the promoter of HoxC13. Knockout Bmi-1 results in significant loss of H2A ubiquitylation and upregulation of Hoxc13 expression, whereas EZH2-mediated H3-K27 methylation is not affected. Our results suggest that EZH2-mediated H3-K27 methylation functions upstream of PRC1 and establishes a critical role for Bmi-1 and Ring1A in H2A ubiquitylation and Hox gene silencing.
AB - Polycomb group (PcG) proteins exist in at least two biochemically distinct protein complexes, the EED-EZH2 complex and the PRC1 complex, that respectively possess H3-K27 methyltransferase and H2A-K119 ubiquitin E3 ligase activities. How the enzymatic activities are regulated and what their role is in Hox gene silencing are not clear. Here, we demonstrate that Bmi-1 and Ring1A, two components of the PRC1 complex, play important roles in H2A ubiquitylation and Hox gene silencing. We show that both proteins positively regulate H2A ubiquitylation. Chromatin immunoprecipitation (ChIP) assays demonstrate that Bmi-1 and other components of the two PcG complexes bind to the promoter of HoxC13. Knockout Bmi-1 results in significant loss of H2A ubiquitylation and upregulation of Hoxc13 expression, whereas EZH2-mediated H3-K27 methylation is not affected. Our results suggest that EZH2-mediated H3-K27 methylation functions upstream of PRC1 and establishes a critical role for Bmi-1 and Ring1A in H2A ubiquitylation and Hox gene silencing.
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U2 - 10.1016/j.molcel.2005.12.002
DO - 10.1016/j.molcel.2005.12.002
M3 - Article
C2 - 16359901
AN - SCOPUS:29144487990
SN - 1097-2765
VL - 20
SP - 845
EP - 854
JO - Molecular Cell
JF - Molecular Cell
IS - 6
ER -