title: Cotranscriptional histone H2B monoubiquitylation is tightly coupled with RNA polymerase II elongation rate.
abstract: Various histone modifications decorate nucleosomes within transcribed genes. Among these, monoubiquitylation of histone H2B (H2Bub1) and methylation of histone H3 on lysines 36 (H3K36me2/3) and 79 (H3K79me2/3) correlate positively with gene expression. By measuring the progression of the transcriptional machinery along genes within live cells, we now report that H2B monoubiquitylation occurs cotranscriptionally and accurately reflects the advance of RNA polymerase II (Pol II). In contrast, H3K36me3 and H3K79me2 are less dynamic and represent Pol II movement less faithfully. High-resolution ChIP-seq reveals that H2Bub1 levels are selectively reduced at exons and decrease in an exon-dependent stepwise manner toward the 3' end of genes. Exonic depletion of H2Bub1 in gene bodies is highly correlated with Pol II pausing at exons, suggesting elongation rate changes associated with intron-exon structure. In support of this notion, H2Bub1 levels were found to be significantly correlated with transcription elongation rates measured in various cell lines. Overall, our data shed light on the organization of H2Bub1 within transcribed genes and single out H2Bub1 as a reliable marker for ongoing transcription elongation.
authors: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel;
authors: Gilad
authors: G
authors: Fuchs
authors: Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv 69978, Israel;
authors: Dror
authors: D
authors: Hollander
authors: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
authors: Yoav
authors: Y
authors: Voichek
authors: Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv 69978, Israel;
authors: Gil
authors: G
authors: Ast
authors: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel; moshe.oren@weizmann.ac.il.
authors: Moshe
authors: M
authors: Oren
mesh_terms: D045744:Cell Line, Tumor; D005091:Exons; D006367:HeLa Cells; D006657:Histones / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D012319:RNA Polymerase II / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D017422:Sequence Analysis, DNA; D061805:Transcription Elongation, Genetic; D054875:Ubiquitination
chemical_list: D006657:Histones; D012333:RNA, Messenger; D012319:RNA Polymerase II