Histone H2Bub1 deubiquitylation is essential for mouse development, but does not regulate global RNA [ChIP-Seq]

The deubiquitinating module (DUBm) of mammalian SAGA complex is composed of the ubiquitin-specific protease 22 (USP22) and ATXN7, ATXN7L3 and ENY2 adaptor proteins, which are all needed for the full activity of USP22 enzyme. In addition, ATXN7L3 is critical for directing the DUB module substrate specificity towards H2Bub1. We reported that USP22 and ATXN7L3 are essential for normal embryonic development of mice, however their requirements are not identical during this process. Global histone H2Bub1 levels were only slightly affected in Usp22 null embryos, while in contrast H2Bub1 levels were strongly increased in Atxn7l3 null mutants and derived cellular systems. Interestingly, the strong H2Bub1 increases observed in the Atxn7l3-/- mouse embryonic stem cells, or Atxn7l3-/- mouse embryonic fibroblasts, do not correlate with the modest genome-wide Pol II occupancy changes observed in the two knock-out cellular systems. Thus, histone H2Bub1 deubiquitylation does not directly regulate global RNA polymerase II transcription. Overall design: Genome-wide investigation of the role of H2Bub in mouse embryonic stem cells (mESCs) and mouse primary embryonic fibroblasts (MEF) cells