MacroH2A1.1 and PARP-1 cooperate to regulate transcription by promoting CBP-mediated H2B acetylation.

Abstract

The histone variant macroH2A1 regulates gene expression important for differentiation, stem-cell reprogramming and tumor suppression. Here, we demonstrate that in primary human cells, macroH2A1 participates in two physically and functionally distinct types of chromatin marked by either H3K27me3 or nine histone acetylations. Using RNA sequencing, we found that macroH2A1-regulated genes, which have roles in cancer progression, are specifically found in macroH2A1-containing acetylated chromatin. Of the two macroH2A1 variants, macroH2A1.1 and macroH2A1.2, the former is suppressed in cancer and can interact with PARP-generated poly(ADP-ribose). Through the recruitment of PARP-1, macroH2A1.1 promotes the CBP-mediated acetylation of H2B K12 and K120, which either positively or negatively regulates the expression of macroH2A1-target genes. Although macroH2A1-regulated H2B acetylation is a common feature of primary cells, this regulation is typically lost in cancer cells. Consequently, our results provide insight into macroH2A1.1's role in cancer suppression.

• Authors: Hongshan Chen, Penelope D Ruiz, Leonid Novikov, Alyssa D Casill, Jong Woo Park, Matthew J Gamble
• Journal: Nature structural & molecular biology (Nat Struct Mol Biol) Vol. 21 Issue 11 Pg. 981-9 (Nov 2014) ISSN: 1545-9985 [Electronic] United States
• PMID: 25306110 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Chromatin
• Histones
• Peptide Fragments
• Protein Isoforms
• Sialoglycoproteins
• bone sialoprotein (35-62), human
• macroH2A histone
• PARP1 protein, human
• Poly (ADP-Ribose) Polymerase-1
• Poly(ADP-ribose) Polymerases

Topics

• Acetylation
• Binding Sites
• Cell Line, Transformed
• Cell Line, Tumor
• Chromatin (metabolism, pathology)
• Fetus
• Fibroblasts (metabolism, pathology)
• Gene Expression Regulation, Neoplastic
• Histones (genetics, metabolism)
• Humans
• Lung (metabolism, pathology)
• Peptide Fragments (genetics, metabolism)
• Poly (ADP-Ribose) Polymerase-1
• Poly(ADP-ribose) Polymerases (genetics, metabolism)
• Protein Binding
• Protein Isoforms (genetics, metabolism)
• Sialoglycoproteins (genetics, metabolism)
• Signal Transduction
• Transcription, Genetic