Histone Ubiquitination: Triggering Gene Activity Vikki M. Weake, Jerry L. Workman  Molecular Cell  Volume 29, Issue 6, Pages 653-663 (March 2008) DOI: 10.1016/j.molcel.2008.02.014 Copyright © 2008 Elsevier Inc. Terms and Conditions

Figure 1 H2B Ubiquitination Requires Early Steps in Transcription Elongation (A) The H2B ubiquitin ligase Bre1 interacts with acidic activators, such as Gal4, and recruits Rad6 and presumably its binding partner Lge1 to target promoters. (B) Monoubiquitination of H2B by Rad6/Bre1 requires interactions with the PAF complex, the BUR complex, and the elongating form of RNA polymerase II that has been phosphorylated on Ser-5 of the CTD by Kin28. The BUR complex phosphorylates Ser-120 of Rad6, which might stimulate its ubiquitin conjugase activity. (C) H2B ubiquitination is required for the recruitment of the Cps35 subunit of COMPASS, which activates di- and trimethylation of Lys-4 H3 by Set1. The 19S proteasome and Ccr4-Not complex also link H2B ubiquitination to Lys-4 H3 methylation by mechanisms that are less clear. Molecular Cell 2008 29, 653-663DOI: (10.1016/j.molcel.2008.02.014) Copyright © 2008 Elsevier Inc. Terms and Conditions

Figure 2 UbH2B Deubiquitination Is Required for Later Stages of Transcription Elongation (A) In the absence of the ubH2B deubiquitinase Ubp8, persistent ubH2B inhibits recruitment of the Ctk1 kinase. (B) Ubp8, within SAGA, deubiquitinates ubH2B, enabling Ctk1 recruitment and phosphorylation of Ser-2 within the CTD of RNA polymerase II. (C) Deletion of the ubiquitin ligase Bre1 and the subsequent lack of ubH2B restores Ctk1 recruitment and Ser-2 phosphorylation even in yeast lacking Ubp8. Molecular Cell 2008 29, 653-663DOI: (10.1016/j.molcel.2008.02.014) Copyright © 2008 Elsevier Inc. Terms and Conditions

Figure 3 H2A Ubiquitin Ligases Are Associated with Repressive Complexes (A) The H2A ubiquitin ligase Ring1B is a component of three different repressive complexes: PRC1 localizes to trimethylated Lys-27 H3 and represses Hox gene transcription; E2F6.com-1 methylates Lys-9 H3 and binds E2F- and myc-response elements; and the FBXL10-BcoR complex contains the Lys-4 H3 demethylase KDM2B and putative additional proteins (dashed lines) and represses BCL6-target genes. (B) The 2A-HUB H2A ubiquitin ligase associates with the NCoR/HDAC1/3 repressive complex and inhibits FACT recruitment and transcription elongation. Conversely, the 2A-DUB ubH2A deubiquitinase associates with the PCAF/KAT2B coactivator and is required for gene activation at a subset of chemokine gene promoters, potentially by enhancing FACT recruitment. Molecular Cell 2008 29, 653-663DOI: (10.1016/j.molcel.2008.02.014) Copyright © 2008 Elsevier Inc. Terms and Conditions