Mammalian SWI/SNF--a subunit BAF250/ARID1 is an E3 ubiquitin ligase that targets histone H2B.
The mammalian SWI/SNF chromatin-remodeling complex facilitates DNA access by transcription factors and the transcription machinery. The characteristic member of human SWI/SNF-A is BAF250/ARID1, of which there are two isoforms, BAF250a/ARID1a and BAF250b/ARID1b. Here we report that BAF250b complexes purified from mammalian cells contain elongin C (Elo C), a BC box binding component of an E3 ubiquitin ligase. BAF250b was found to have a BC box motif, associate with Elo C in a BC box-dependent manner, and, together with cullin 2 and Roc1, assemble into an E3 ubiquitin ligase. The BAF250b BC box mutant protein was unstable in vivo and was autoubiquitinated in a manner similar to that for the VHL BC box mutants. The discovery that BAF250 is part of an E3 ubiquitin ligase adds an enzymatic function to the chromatin-remodeling complex SWI/SNF-A. The immunopurified BAF250b E3 ubiquitin ligase was found to target histone H2B at lysine 120 for monoubiquitination in vitro. To date, all H2B monoubiquitination was attributed to the human homolog of yeast Bre1 (RNF20/40). Mutation of Drosophila osa, the homolog of BAF250, or depletion of BAF250 by RNA interference (RNAi) in cultured human cells resulted in global decreases in monoubiquitinated H2B, implicating BAF250 in the cross talk of histone modifications.
Li
Xuan Shirley
XS
Department of Microbiology, Howard Hughes Medical Institute, NYU School of Medicine, 550 First Avenue, New York, NY 10016, USA.
Trojer
Patrick
P
Matsumura
Tatsushi
T
Treisman
Jessica E
JE
Tanese
Naoko
N
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D044842:Cullin Proteins / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins; D004331:Drosophila melanogaster / Q000033:anatomy & histology / Q000502:physiology; D000075065:Elongin; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
C112476:ARID1A protein, human; C105153:CUL2 protein, human; D002352:Carrier Proteins; D044842:Cullin Proteins; D004268:DNA-Binding Proteins; C000616395:ELOC protein, human; D000075065:Elongin; D006657:Histones; D009687:Nuclear Proteins; D021122:Protein Subunits; C479529:RBX1 protein, human; D034741:RNA, Small Interfering; D014157:Transcription Factors; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex