Histone crosstalk between H2B monoubiquitination and H3 methylation mediated by COMPASS.
COMPASS, the yeast homolog of the mammalian MLL complex, is a histone H3 lysine 4 (H3K4) methylase consisting of Set1 (KMT2) and seven other polypeptides, including Cps35, the only essential subunit. Histone H2B monoubiquitination by Rad6/Bre1 is required for both H3K4 methylation by COMPASS, and H3K79 methylation by Dot1. However, the molecular mechanism for such histone crosstalk is poorly understood. Here, we demonstrate that histone H2B monoubiquitination controls the binding of Cps35 with COMPASS complex. Cps 35 is required for COMPASS' catalytic activity in vivo, and the addition of exogenous purified Cps35 to COMPASS purified from a Deltarad6 background results in the generation of a methylation competent COMPASS. Cps35 associates with the chromatin of COMPASS-regulated genes in a H2BK123 monoubiquitination-dependent but Set1-independent manner. Cps35 is also required for proper H3K79 trimethylation. These findings offer insight into the molecular role of Cps35 in translating the H2B monoubiquitination signal into H3 methylation.
Lee
Jung-Shin
JS
Stowers Institute for Medical Research, 1000 East 50(th) Street, Kansas City, MO 64110, USA.
Shukla
Abhijit
A
Schneider
Jessica
J
Swanson
Selene K
SK
Washburn
Michael P
MP
Florens
Laurence
L
Bhaumik
Sukesh R
SR
Shilatifard
Ali
A
D002843:Chromatin; D004268:DNA-Binding Proteins / Q000378:metabolism; D004795:Enzyme Stability; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D008745:Methylation; D046912:Multiprotein Complexes / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D021122:Protein Subunits; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism; D054875:Ubiquitination
D002843:Chromatin; D004268:DNA-Binding Proteins; D006657:Histones; D046912:Multiprotein Complexes; D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D011495:Histone-Lysine N-Methyltransferase; C411250:SET1 protein, S cerevisiae; C484873:SWD2 protein, S cerevisiae; C471606:RAD6 protein, S cerevisiae; D044763:Ubiquitin-Conjugating Enzymes