Polycomb group and SCF ubiquitin ligases are found in a novel BCOR complex that is recruited to BCL6 targets.
The corepressor BCOR potentiates transcriptional repression by the proto-oncoprotein BCL6 and suppresses the transcriptional activity of a common mixed-lineage leukemia fusion partner, AF9. Mutations in human BCOR cause male lethal, X-linked oculofaciocardiodental syndrome. We identified a BCOR complex containing Polycomb group (PcG) and Skp-Cullin-F-box subcomplexes. The PcG proteins include RING1, RYBP, NSPC1, a Posterior Sex Combs homolog, and RNF2, an E3 ligase for the mono-ubiquitylation of H2A. BCOR complex components and mono-ubiquitylated H2A localize to BCL6 targets, indicating that the BCOR complex employs PcG proteins to expand the repertoire of enzymatic activities that can be recruited by BCL6. This also suggests that BCL6 can target PcG proteins to DNA. In addition, the BCOR complex contains components of a second ubiquitin E3 ligase, namely, SKP1 and FBXL10 (JHDM1B). We show that BCOR coimmunoprecipitates isoforms of FBXL10 which contain a JmjC domain that recently has been determined to have histone H3K36 demethylase activity. The recruitment of two distinct classes of E3 ubiquitin ligases and a histone demethylase by BCOR suggests that BCOR uses a unique combination of epigenetic modifications to direct gene silencing.
Gearhart
Micah D
MD
Department of Genetics, Cell Biology and Development, 6-160 Jackson Hall, 321 Church Street SE, Minneapolis, MN 55455, USA.
Corcoran
Connie M
CM
Wamstad
Joseph A
JA
Bardwell
Vivian J
VJ
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D002877:Chromosomes, Human / Q000235:genetics; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D051379:Mice; D063150:Polycomb Repressive Complex 1; D063146:Polycomb-Group Proteins; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D025941:Protein Interaction Mapping; D021381:Protein Transport; D011518:Proto-Oncogene Proteins / Q000302:isolation & purification / Q000378:metabolism*; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000378:metabolism*; D012097:Repressor Proteins / Q000302:isolation & purification / Q000378:metabolism*; D044843:SKP Cullin F-Box Protein Ligases / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology; D014327:Trophoblasts / Q000166:cytology; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
C411984:BCOR protein, human; D002352:Carrier Proteins; D006657:Histones; C496334:PCGF1 protein, human; D063146:Polycomb-Group Proteins; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D012097:Repressor Proteins; D025801:Ubiquitin; D063150:Polycomb Repressive Complex 1; D044843:SKP Cullin F-Box Protein Ligases; D044767:Ubiquitin-Protein Ligases