Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Genes Dev. 2003 Nov 1;17(21):2648-63. Epub 2003 Oct 16.

Transcriptional activation via sequential histone H2B ubiquitylation and deubiquitylation, mediated by SAGA-associated Ubp8.

Author information

  • 1The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.

Abstract

Gene activation and repression regulated by acetylation and deacetylation represent a paradigm for the function of histone modifications. We provide evidence that, in contrast, histone H2B monoubiquitylation and its deubiquitylation are both involved in gene activation. Substitution of the H2B ubiquitylation site at Lys 123 (K123) lowered transcription of certain genes regulated by the acetylation complex SAGA. Gene-associated H2B ubiquitylation was transient, increasing early during activation, and then decreasing coincident with significant RNA accumulation. We show that Ubp8, a component of the SAGA acetylation complex, is required for SAGA-mediated deubiquitylation of histone H2B in vitro. Loss of Ubp8 in vivo increased both gene-associated and overall cellular levels of ubiquitylated H2B. Deletion of Ubp8 lowered transcription of SAGA-regulated genes, and the severity of this defect was exacerbated by codeletion of the Gcn5 acetyltransferase within SAGA. In addition, disruption of either ubiquitylation or Ubp8-mediated deubiquitylation of H2B resulted in altered levels of gene-associated H3 Lys 4 methylation and Lys 36 methylation, which have both been linked to transcription. These results suggest that the histone H2B ubiquitylation state is dynamic during transcription, and that the sequence of histone modifications helps to control transcription.

PMID:
14563679
[PubMed - indexed for MEDLINE]
PMCID:
PMC280615
Free PMC Article

Images from this publication.See all images (7)Free text

Figure 1.
Figure 2.
Figure 3.
Figure 5.
Figure 4.
Figure 6.
Figure 7.
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for HighWire Icon for PubMed Central Icon for Faculty of 1000
    Loading ...
    Write to the Help Desk