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

Hongshan Chen, Penelope D. Ruiz, Leonid Novikov, Alyssa D. Casill, Jong Woo Park, Matthew J. Gamble

Research output: Contribution to journalArticle

44 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)981-989
Number of pages9
JournalNature Structural and Molecular Biology
Volume21
Issue number11
DOIs
StatePublished - Nov 13 2014

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Acetylation
Neoplasms
Histones
Chromatin
Poly Adenosine Diphosphate Ribose
RNA Sequence Analysis
Genes
Stem Cells
Gene Expression

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology
  • Medicine(all)

Cite this

MacroH2A1.1 and PARP-1 cooperate to regulate transcription by promoting CBP-mediated H2B acetylation. / Chen, Hongshan; Ruiz, Penelope D.; Novikov, Leonid; Casill, Alyssa D.; Park, Jong Woo; Gamble, Matthew J.

In: Nature Structural and Molecular Biology, Vol. 21, No. 11, 13.11.2014, p. 981-989.

Research output: Contribution to journalArticle

Chen, Hongshan ; Ruiz, Penelope D. ; Novikov, Leonid ; Casill, Alyssa D. ; Park, Jong Woo ; Gamble, Matthew J. / MacroH2A1.1 and PARP-1 cooperate to regulate transcription by promoting CBP-mediated H2B acetylation. In: Nature Structural and Molecular Biology. 2014 ; Vol. 21, No. 11. pp. 981-989.
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