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

doi:10.1038/nsmb.2903

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 journal › Article › peer-review

92 Scopus citations

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 language	English (US)
Pages (from-to)	981-989
Number of pages	9
Journal	Nature Structural and Molecular Biology
Volume	21
Issue number	11
DOIs	https://doi.org/10.1038/nsmb.2903
State	Published - Nov 13 2014

ASJC Scopus subject areas

Structural Biology
Molecular Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/nsmb.2903

Cite this

@article{6b6878e606bc4a77862f38620ee38248,

title = "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.",

author = "Hongshan Chen and Ruiz, {Penelope D.} and Leonid Novikov and Casill, {Alyssa D.} and Park, {Jong Woo} and Gamble, {Matthew J.}",

note = "Funding Information: We thank S.B. Horwitz, C.S. Rubin, J.M. Backer and C.W. Chow from Albert Einstein College of Medicine for sharing equipment and reagents. We thank T. Zhang (Regeneron Pharmaceuticals) for critical reading of the manuscript. The high-throughput sequencing was performed by the Einstein Epigenomics Core Facility. We thank specimen donors and The Cancer Genome Atlas (TCGA) genome characterization center at the University of North Carolina for their contributions to the lung squamous-cell carcinoma data set from TCGA. This work was supported by the US National Institutes of Health training grant T32GM007491-38 (P.D.R.) and grant R01CA155232 (M.J.G.).",

year = "2014",

month = nov,

day = "13",

doi = "10.1038/nsmb.2903",

language = "English (US)",

volume = "21",

pages = "981--989",

journal = "Nature Structural and Molecular Biology",

issn = "1545-9993",

publisher = "Nature Publishing Group",

number = "11",

}

TY - JOUR

T1 - MacroH2A1.1 and PARP-1 cooperate to regulate transcription by promoting CBP-mediated H2B acetylation

AU - Chen, Hongshan

AU - Ruiz, Penelope D.

AU - Novikov, Leonid

AU - Casill, Alyssa D.

AU - Park, Jong Woo

AU - Gamble, Matthew J.

N1 - Funding Information: We thank S.B. Horwitz, C.S. Rubin, J.M. Backer and C.W. Chow from Albert Einstein College of Medicine for sharing equipment and reagents. We thank T. Zhang (Regeneron Pharmaceuticals) for critical reading of the manuscript. The high-throughput sequencing was performed by the Einstein Epigenomics Core Facility. We thank specimen donors and The Cancer Genome Atlas (TCGA) genome characterization center at the University of North Carolina for their contributions to the lung squamous-cell carcinoma data set from TCGA. This work was supported by the US National Institutes of Health training grant T32GM007491-38 (P.D.R.) and grant R01CA155232 (M.J.G.).

PY - 2014/11/13

Y1 - 2014/11/13

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84908875248&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84908875248&partnerID=8YFLogxK

U2 - 10.1038/nsmb.2903

DO - 10.1038/nsmb.2903

M3 - Article

C2 - 25306110

AN - SCOPUS:84908875248

SN - 1545-9993

VL - 21

SP - 981

EP - 989

JO - Nature Structural and Molecular Biology

JF - Nature Structural and Molecular Biology

IS - 11

ER -

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

Abstract

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this