Article

Histone H2B C-terminal helix mediates trans-histone H3K4 methylation independent of H2B ubiquitination.

Department of Biochemistry, Vanderbilt University School of Medicine, 613C Light Hall, Nashville, TN 37232, USA.
Molecular and Cellular Biology (Impact Factor: 5.04). 07/2010; 30(13):3216-32. DOI: 10.1128/MCB.01008-09
Source: PubMed

ABSTRACT The trans-histone regulatory cross talk between H2BK123 ubiquitination (H2Bub1) and H3K4 and H3K79 methylation is not fully understood. In this study, we report that the residues arginine 119 and threonine 122 in the H2B C-terminal helix are important for transcription and cell growth and play a direct role in controlling H2Bub1 and H3K4 methylation. These residues modulate H2Bub1 levels by controlling the chromatin binding and activities of the deubiquitinases. Furthermore, we find an uncoupling of the H2Bub1-mediated coregulation of both H3K4 and -K79 methylation, as these H2B C-terminal helix residues are part of a distinct surface that affects only Set1-COMPASS (complex proteins associated with Set1)-mediated H3K4 methylation without affecting the functions of Dot1. Importantly, we also find that these residues interact with Spp1 and control the chromatin association, integrity, and overall stability of Set1-COMPASS independent of H2Bub1. Therefore, we have uncovered a novel role for the H2B C-terminal helix in the trans-histone cross talk as a binding surface for Set1-COMPASS. We provide further insight into the trans-histone cross talk and propose that H2Bub1 stabilizes the nucleosome by preventing H2A-H2B eviction and, thereby, retains the "docking site" for Set1-COMPASS on chromatin to maintain its stable chromatin association, complex stability, and processive methylation.

0 Followers
 · 
90 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Increasing evidence suggests that linker histone H1 can influence distinct cellular processes by acting as a gene-specific regulator. However, the mechanistic basis underlying such H1 specificity and whether H1 acts in concert with other chromatin-altering activities remain unclear. Here, we show that one of the H1 subtypes, H1.2, stably interacts with Cul4A E3 ubiquitin ligase and PAF1 elongation complexes and that such interaction potentiates target gene transcription via induction of H4K31ubiquitylation, H3K4me3, and H3K79me2. H1.2, Cul4A, and PAF1 are functionally cooperative because their individual knockdown results in the loss of the corresponding histone marks and the deficiency of target gene transcription. H1.2 interacts with the serine 2-phosphorylated form of RNAPII, and we argue that it recruits the Cul4A and PAF1 complexes to target genes by bridging the interaction between the Cul4A and PAF1 complexes. These data define an expanded role for H1 in regulating gene transcription and illustrate its dependence on the elongation competence of RNAPII.
    Cell Reports 12/2013; DOI:10.1016/j.celrep.2013.11.038 · 7.21 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Past studies have documented a crosstalk between H2B ubiquitylation (H2Bub) and H3K4 methylation, but little (if any) direct evidence exists explaining the mechanism underlying H2Bub-dependent H3K4 methylation on chromatin templates. Here, we took advantage of an in vitro histone methyltransferase assay employing a reconstituted yeast Set1 complex (ySet1C) and a recombinant chromatin template containing fully ubiquitylated H2B to gain valuable insights. Combined with genetic analyses, we demonstrate that the n-SET domain within Set1, but not Swd2, is essential for H2Bub-dependent H3K4 methylation. Spp1, a homolog of human CFP1, is conditionally involved in this crosstalk. Our findings extend to the human Set1 complex, underscoring the conserved nature of this disease-relevant crosstalk pathway. As not all members of the H3K4 methyltransferase family contain n-SET domains, our studies draw attention to the n-SET domain as a predictor of an H2B ubiquitylation-sensing mechanism that leads to downstream H3K4 methylation.
    Molecular cell 02/2013; DOI:10.1016/j.molcel.2013.01.034 · 14.46 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In Saccharomyces cerevisiae, subtelomeric silencing is involved in the propagation of Silent Information Regulator (SIR) proteins toward euchromatin. Numerous mechanisms are involved in antagonizing the local spread of Sir-dependent silent chromatin into neighboring euchromatin. Here, we identified a novel role for sumoylation E3 ligase Mms21 in the maintenance of subtelomeric silencing. We found that disruption of E3 ligase activity of Mms21 results in the de-repression of subtelomeric silencing. Deletion of E3 ligase domain of Mms21 led to decreased binding of Sir2p, Sir3p and Sir4 at subtelomeric chromatins and increased H3K4 tri-methylation at telomere-distal euchromatin regions, correlating with increased gene expression in two subtelomeric reporter genes. In addition, a mms21Δsl mutant caused a severe growth defect in combination with htz1Δ deletion and showed an enhanced association of Htz1 with telomere proximal regions. Taken together, our findings suggest an important role of Mms21p; it contributes to subtelomeric silencing during the formation of a heterochromatin boundary.
    Biochemical and Biophysical Research Communications 07/2013; DOI:10.1016/j.bbrc.2013.07.096 · 2.28 Impact Factor