MCM2 promotes symmetric inheritance of modified histones during DNA replication

Nataliya Petryk; Maria Dalby; Alice Wenger; Caroline B. Stromme; Anne Strandsby; Robin Andersson; Anja Groth

doi:10.1126/science.aau0294

MCM2 promotes symmetric inheritance of modified histones during DNA replication

Nataliya Petryk, Maria Dalby, Alice Wenger, Caroline B. Stromme, Anne Strandsby, Robin Andersson, Anja Groth

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Abstract

During genome replication, parental histones are recycled to newly replicated DNA with their posttranslational modifications (PTMs). It remains unknown whether sister chromatids inherit modified histones evenly. Here, we measured histone PTM partition to sister chromatids in embryonic stem cells. We found that parental histones H3-H4 segregate to both daughter DNA strands with a weak leading strand bias, skewing partition at topologically associating domain (TAD) borders and enhancers proximal to replication initiation zones. Segregation of parental histones to the leading strand increased markedly in cells with histone-binding mutations in MCM2, part of the replicative helicase, exacerbating histone PTM sister chromatid asymmetry. This work reveals how histones are inherited to sister chromatids and identifies a mechanism for how symmetric cell division is ensured by the replication machinery.

Original language	English
Journal	Science
Volume	361
Issue number	6409
Pages (from-to)	1389-1392
Number of pages	3
ISSN	0036-8075
DOIs	https://doi.org/10.1126/science.aau0294
Publication status	Published - 2018

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title = "MCM2 promotes symmetric inheritance of modified histones during DNA replication",

abstract = "During genome replication, parental histones are recycled to newly replicated DNA with their posttranslational modifications (PTMs). It remains unknown whether sister chromatids inherit modified histones evenly. Here, we measured histone PTM partition to sister chromatids in embryonic stem cells. We found that parental histones H3-H4 segregate to both daughter DNA strands with a weak leading strand bias, skewing partition at topologically associating domain (TAD) borders and enhancers proximal to replication initiation zones. Segregation of parental histones to the leading strand increased markedly in cells with histone-binding mutations in MCM2, part of the replicative helicase, exacerbating histone PTM sister chromatid asymmetry. This work reveals how histones are inherited to sister chromatids and identifies a mechanism for how symmetric cell division is ensured by the replication machinery.",

author = "Nataliya Petryk and Maria Dalby and Alice Wenger and Stromme, {Caroline B.} and Anne Strandsby and Robin Andersson and Anja Groth",

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doi = "10.1126/science.aau0294",

language = "English",

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pages = "1389--1392",

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T1 - MCM2 promotes symmetric inheritance of modified histones during DNA replication

AU - Petryk, Nataliya

AU - Dalby, Maria

AU - Wenger, Alice

AU - Stromme, Caroline B.

AU - Strandsby, Anne

AU - Andersson, Robin

AU - Groth, Anja

PY - 2018

Y1 - 2018

N2 - During genome replication, parental histones are recycled to newly replicated DNA with their posttranslational modifications (PTMs). It remains unknown whether sister chromatids inherit modified histones evenly. Here, we measured histone PTM partition to sister chromatids in embryonic stem cells. We found that parental histones H3-H4 segregate to both daughter DNA strands with a weak leading strand bias, skewing partition at topologically associating domain (TAD) borders and enhancers proximal to replication initiation zones. Segregation of parental histones to the leading strand increased markedly in cells with histone-binding mutations in MCM2, part of the replicative helicase, exacerbating histone PTM sister chromatid asymmetry. This work reveals how histones are inherited to sister chromatids and identifies a mechanism for how symmetric cell division is ensured by the replication machinery.

AB - During genome replication, parental histones are recycled to newly replicated DNA with their posttranslational modifications (PTMs). It remains unknown whether sister chromatids inherit modified histones evenly. Here, we measured histone PTM partition to sister chromatids in embryonic stem cells. We found that parental histones H3-H4 segregate to both daughter DNA strands with a weak leading strand bias, skewing partition at topologically associating domain (TAD) borders and enhancers proximal to replication initiation zones. Segregation of parental histones to the leading strand increased markedly in cells with histone-binding mutations in MCM2, part of the replicative helicase, exacerbating histone PTM sister chromatid asymmetry. This work reveals how histones are inherited to sister chromatids and identifies a mechanism for how symmetric cell division is ensured by the replication machinery.

U2 - 10.1126/science.aau0294

DO - 10.1126/science.aau0294

M3 - Journal article

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VL - 361

SP - 1389

EP - 1392

JO - Science

JF - Science

SN - 0036-8075

IS - 6409

ER -

MCM2 promotes symmetric inheritance of modified histones during DNA replication

Abstract

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