Chromatin posttranslational modifications (PTMs), including monoubiquitylation of histone H2B on lysine 120 (H2Bub1), play a major role in regulating genome functions. To elucidate the molecular mechanisms of H2Bub1 activity, a chromatin template uniformly containing H2Bub1 was used as an affinity matrix to identify preferentially interacting human proteins. Over 90 such factors were found, including proteins and protein complexes associated with transcription, RNA posttranscriptional modifications, and DNA replication and repair. Notably, we found that the SWI/SNF chromatin remodeling complex associates preferentially with H2Bub1-rich chromatin. Moreover,SWI/SNF is required for optimal transcription of a subset of genes that are selectively dependent on H2Bub1. Our findings substantially expand the known H2Bub1 interactome and provide insights into the functions of this PTM in mammalian gene regulation
Bibliographical noteFunding Information:
We are grateful to Moshe Yaniv, Frauke Melchior, Steven Bergink, Gilad Fuchs, Eran Kotler, and Lior Golomb for helpful discussions. We thank Tamar Unger and Shira Albeck for preparing H2B and ubiquitin and Uwe Plessmann and Monika Raabe for expert technical assistance. This work was supported in part by grant 293438 (RUBICAN) from the European Research Council (to M.O.), grant R37 CA40099 from the National Cancer Institute (to M.O.), the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (to M.O.), the Edmond J. Safra Foundation (A.B.), the Lower Saxony-Israeli Association (to M.O. and W.F.), the Max Planck Society (to H.U. and W.F.), and the Mina and James Heinemann Foundation (to W.F.). M.O. is the incumbent of the Andre Lwoff chair in molecular biology. E.S. is supported by the Adams Fellowship Program of the Israel Academy of Sciences and Humanities. M.N. is supported by a fellowship from the MSc/PhD program “Molecular Biology” International Max Planck Research School at the Georg August University, Göttingen.
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology