Parental nucleosome segregation and the inheritance of cellular identity

Escobar, Thelma M.; Loyola, Alejandra; Reinberg, Danny

doi:10.1038/s41576-020-00312-w

Cited by 84 publications

(104 citation statements)

References 159 publications

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“…The integrity of Polycomb chromatin domains is challenged by passage of the replication machinery which displaces parental nucleosomes from DNA and necessitates the incorporation of new unmodified histones and the reincorporation of modified parental histones into the replicated daughter strands 164 , 165 . Communication and feedback mechanisms inherent to Polycomb complexes 32 , 127 could in theory support copying and epigenetic maintenance of Polycomb chromatin domains, but this would rely on modified parental nucleosomes being deposited in the same location on daughter strands.…”

Section: Introductionmentioning

confidence: 99%

The molecular principles of gene regulation by Polycomb repressive complexes

Blackledge

Klose

2021

Nat Rev Mol Cell Biol

257

237

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Precise control of gene expression is fundamental to cell function and development. Although ultimately gene expression relies on DNA-binding transcription factors to guide the activity of the transcription machinery to genes, it has also become clear that chromatin and histone post-translational modification have fundamental roles in gene regulation. Polycomb repressive complexes represent a paradigm of chromatin-based gene regulation in animals. The Polycomb repressive system comprises two central protein complexes, Polycomb repressive complex 1 (PRC1) and PRC2, which are essential for normal gene regulation and development. Our early understanding of Polycomb function relied on studies in simple model organisms, but more recently it has become apparent that this system has expanded and diverged in mammals. Detailed studies are now uncovering the molecular mechanisms that enable mammalian PRC1 and PRC2 to identify their target sites in the genome, communicate through feedback mechanisms to create Polycomb chromatin domains, and control transcription to regulate gene expression. In this Review, we discuss and contextualise the emerging principles that define how this fascinating chromatin-based system regulates gene expression in mammals.

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Section: Introductionmentioning

confidence: 99%

The molecular principles of gene regulation by Polycomb repressive complexes

Blackledge

Klose

2021

Nat Rev Mol Cell Biol

257

237

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“…The molecular mechanisms by which newly synthesized histones are incorporated onto DNA have been well studied, but little is known about how pre‐existing old histones are re‐incorporated during DNA replication followed by segregation during cell division (Alabert & Groth, 2012; Ahmad & Henikoff, 2018; Serra‐Cardona & Zhang, 2018). Recent studies have shed light on both the molecular mechanisms (Gan et al, 2018; Petryk et al, 2018; Yu et al, 2018) and the cellular responses (Lin et al, 2016; Reveron‐Gomez et al, 2018; Escobar et al, 2019) for old histone recycling in symmetrically dividing cells [reviewed by Escobar et al (2021)]. However, it remains elusive how these processes are regulated in asymmetrically dividing cells, including many types of adult stem cells.…”

Section: Introductionmentioning

confidence: 99%

Characterization of histone inheritance patterns in the Drosophila female germline

et al. 2021

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Stem cells have the unique ability to undergo asymmetric division which produces two daughter cells that are genetically identical, but commit to different cell fates. The loss of this balanced asymmetric outcome can lead to many diseases, including cancer and tissue dystrophy. Understanding this tightly regulated process is crucial in developing methods to treat these abnormalities. Here, we report that during a Drosophila female germline stem cell asymmetric division, the two daughter cells differentially inherit histones at key genes related to either maintaining the stem cell state or promoting differentiation, but not at constitutively active or silenced genes. We combine histone labeling with DNA Oligopaints to distinguish old versus new histones and visualize their inheritance patterns at a single-gene resolution in asymmetrically dividing cells in vivo. This strategy can be applied to other biological systems involving cell fate change during development or tissue homeostasis in multicellular organisms.

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“…The parental H3/H4 tetramer, which contains most of the epigenetically important modifications such as acetylation and methylation, is recycled onto one of the resulting daughter duplexes near its original location ( 7–14 ). This provides for the spatial memory of the parental histone modification patterns ( 15 , 16 ). These histone modification patterns play a central role in the formation of specific chromatin states by regulating inter-nucleosomal interactions and the association of non-histone proteins with chromatin.…”

Section: Introductionmentioning

confidence: 99%

Epigenetic regulation of nuclear lamina-associated heterochromatin by HAT1 and the acetylation of newly synthesized histones

Popova

Nagarajan

Lovejoy

et al. 2021

Nucleic Acids Research

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A central component of the epigenome is the pattern of histone post-translational modifications that play a critical role in the formation of specific chromatin states. Following DNA replication, nascent chromatin is a 1:1 mixture of parental and newly synthesized histones and the transfer of modification patterns from parental histones to new histones is a fundamental step in epigenetic inheritance. Here we report that loss of HAT1, which acetylates lysines 5 and 12 of newly synthesized histone H4 during replication-coupled chromatin assembly, results in the loss of accessibility of large domains of heterochromatin, termed HAT1-dependent Accessibility Domains (HADs). HADs are mega base-scale domains that comprise ∼10% of the mouse genome. HAT1 globally represses H3 K9 me3 levels and HADs correspond to the regions of the genome that display HAT1-dependent increases in H3 K9me3 peak density. HADs display a high degree of overlap with a subset of Lamin-Associated Domains (LADs). HAT1 is required to maintain nuclear structure and integrity. These results indicate that HAT1 and the acetylation of newly synthesized histones may be critical regulators of the epigenetic inheritance of heterochromatin and suggest a new mechanism for the epigenetic regulation of nuclear lamina-heterochromatin interactions.

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Parental nucleosome segregation and the inheritance of cellular identity

Cited by 84 publications

References 159 publications

The molecular principles of gene regulation by Polycomb repressive complexes

The molecular principles of gene regulation by Polycomb repressive complexes

Characterization of histone inheritance patterns in the Drosophila female germline

Epigenetic regulation of nuclear lamina-associated heterochromatin by HAT1 and the acetylation of newly synthesized histones

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