Retargeting of macroH2A following mitosis to cytogenetic-scale heterochromatic domains

Research output: Contribution to journalArticle

Abstract

The heritability of chromatin states through cell division is a potential contributor to the epigenetic maintenance of cellular memory of prior states. The macroH2A histone variant has properties of a regulator of epigenetic cell memory, including roles controlling gene silencing and cell differentiation. Its mechanisms of regional genomic targeting and maintenance through cell division are unknown. Here, we combined in vivo imaging with biochemical and genomic approaches to show that human macroH2A is incorporated into chromatin in the G1 phase of the cell cycle following DNA replication. The newly incorporated macroH2A retargets the same large heterochromatic domains where macroH2A was already enriched in the previous cell cycle. It remains heterotypic, targeting individual nucleosomes that do not already contain a macroH2A molecule. The pattern observed resembles that of a new deposition of centromeric histone variants during the cell cycle, indicating mechanistic similarities for macrodomain-scale regulation of epigenetic properties of the cell.

Original languageEnglish (US)
Pages (from-to)1810-1823
Number of pages14
JournalThe Journal of cell biology
Volume218
Issue number6
DOIs
StatePublished - Jun 3 2019

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Mitosis
Epigenomics
Cytogenetics
Cell Cycle
Cell Division
Chromatin
Maintenance
Nucleosomes
G1 Phase
Gene Silencing
DNA Replication
Histones
Cell Differentiation

ASJC Scopus subject areas

  • Cell Biology

Cite this

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title = "Retargeting of macroH2A following mitosis to cytogenetic-scale heterochromatic domains",
abstract = "The heritability of chromatin states through cell division is a potential contributor to the epigenetic maintenance of cellular memory of prior states. The macroH2A histone variant has properties of a regulator of epigenetic cell memory, including roles controlling gene silencing and cell differentiation. Its mechanisms of regional genomic targeting and maintenance through cell division are unknown. Here, we combined in vivo imaging with biochemical and genomic approaches to show that human macroH2A is incorporated into chromatin in the G1 phase of the cell cycle following DNA replication. The newly incorporated macroH2A retargets the same large heterochromatic domains where macroH2A was already enriched in the previous cell cycle. It remains heterotypic, targeting individual nucleosomes that do not already contain a macroH2A molecule. The pattern observed resembles that of a new deposition of centromeric histone variants during the cell cycle, indicating mechanistic similarities for macrodomain-scale regulation of epigenetic properties of the cell.",
author = "Hanae Sato and Bin Wu and Fabien Delahaye and Singer, {Robert H.} and Greally, {John M.}",
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AU - Sato, Hanae

AU - Wu, Bin

AU - Delahaye, Fabien

AU - Singer, Robert H.

AU - Greally, John M.

PY - 2019/6/3

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AB - The heritability of chromatin states through cell division is a potential contributor to the epigenetic maintenance of cellular memory of prior states. The macroH2A histone variant has properties of a regulator of epigenetic cell memory, including roles controlling gene silencing and cell differentiation. Its mechanisms of regional genomic targeting and maintenance through cell division are unknown. Here, we combined in vivo imaging with biochemical and genomic approaches to show that human macroH2A is incorporated into chromatin in the G1 phase of the cell cycle following DNA replication. The newly incorporated macroH2A retargets the same large heterochromatic domains where macroH2A was already enriched in the previous cell cycle. It remains heterotypic, targeting individual nucleosomes that do not already contain a macroH2A molecule. The pattern observed resembles that of a new deposition of centromeric histone variants during the cell cycle, indicating mechanistic similarities for macrodomain-scale regulation of epigenetic properties of the cell.

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