H2B ubiquitylation promotes RNA Pol II processivity via PAF1 and pTEFb

Mol Cell. 2014 Jun 19;54(6):920-931. doi: 10.1016/j.molcel.2014.04.013. Epub 2014 May 15.


Histone H2B ubiquitination plays an important role in transcription regulation. It has been shown that H2B ubiquitination is regulated by multiple upstream events associated with elongating RNA polymerase. Here we demonstrate that H2B K34 ubiquitylation by the MOF-MSL complex is part of the protein networks involved in early steps of transcription elongation. Knocking down MSL2 in the MOF-MSL complex affects not only global H2BK34ub, but also multiple cotranscriptionally regulated histone modifications. More importantly, we show that the MSL, PAF1, and RNF20/40 complexes are recruited and stabilized at active gene promoters by direct binary interactions. The stabilized complexes serve to regulate chromatin association of pTEFb through a positive feedback loop and facilitate Pol II transition during early transcription elongation. Results from our biochemical studies are underscored by genome-wide analyses that show high RNA Pol II processivity and transcription activity at MSL target genes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies / immunology
  • Basic-Leucine Zipper Transcription Factors / metabolism*
  • Binding Sites / genetics
  • Cell Line, Tumor
  • Chromatin / genetics
  • Gene Expression Regulation
  • Genome-Wide Association Study
  • HeLa Cells
  • Histone Acetyltransferases / chemistry
  • Histones / chemistry*
  • Histones / immunology
  • Humans
  • Nuclear Proteins / metabolism*
  • Promoter Regions, Genetic
  • Protein Binding / genetics
  • RNA Interference
  • RNA Polymerase II / metabolism*
  • RNA, Small Interfering
  • Transcription Factors
  • Transcription, Genetic
  • Ubiquitin-Protein Ligases / chemistry
  • Ubiquitin-Protein Ligases / genetics*
  • Ubiquitination*


  • Antibodies
  • Basic-Leucine Zipper Transcription Factors
  • Chromatin
  • Histones
  • Nuclear Proteins
  • PAF1 protein, human
  • RNA, Small Interfering
  • TEF protein, human
  • Transcription Factors
  • Histone Acetyltransferases
  • KAT8 protein, human
  • MSL2 protein, human
  • RNF20 protein, human
  • RNF40 protein, human
  • Ubiquitin-Protein Ligases
  • RNA Polymerase II

Associated data

  • GEO/GSE20485
  • GEO/GSE37268