Histone H3.3 incorporation provides a unique and functionally essential telomeric chromatin in embryonic stem cells

Lee H Wong; Hua Ren; Evan J Williams; James Derrick Robert McGhie; Soyeon Ahn; Marcus L J Sim; Angela Tam; Elizabeth Earle; Melissa A Anderson; Jeffrey R Mann; Andy Choo

doi:10.1101/gr.084947.108

Histone H3.3 incorporation provides a unique and functionally essential telomeric chromatin in embryonic stem cells

Lee H Wong, Hua Ren, Evan J Williams, James Derrick Robert McGhie, Soyeon Ahn, Marcus L J Sim, Angela Tam, Elizabeth Earle, Melissa A Anderson, Jeffrey R Mann, Andy Choo

Research output: Contribution to journal › Article › Research › peer-review

140 Citations (Scopus)

Abstract

Little is known about the telomere chromatin dynamics of embryonic stem (ES) cell. Here, we demonstrate localization of histone H3.3 at interphase telomeres and enrichment of Ser31-phosphorylated H3.3 at metaphase telomeres in pluripotent mouse ES cells. Upon differentiation, telomeric H3.3S31P signal decreases, accompanied by increased association of heterochromatin repressive marks and decreased micrococcal nuclease sensitivity at the telomeres. H3.3 is recruited to the telomeres at late S/G2 phase, coinciding with telomere replication and processing. RNAi-depletion of H3.3 induces telomere-dysfunction phenotype, providing evidence for a role of H3.3 in the regulation of telomere chromatin integrity in ES cells. The distinctive changes in H3.3 distribution suggests the existence of a unique and functionally essential telomere chromatin in ES cells that undergoes dynamic differentiation-dependent remodeling during the process of differentiation.

Original language	English
Pages (from-to)	404 - 414
Number of pages	11
Journal	Genome Research
Volume	19
Issue number	3
DOIs	https://doi.org/10.1101/gr.084947.108
Publication status	Published - 2009
Externally published	Yes

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title = "Histone H3.3 incorporation provides a unique and functionally essential telomeric chromatin in embryonic stem cells",

abstract = "Little is known about the telomere chromatin dynamics of embryonic stem (ES) cell. Here, we demonstrate localization of histone H3.3 at interphase telomeres and enrichment of Ser31-phosphorylated H3.3 at metaphase telomeres in pluripotent mouse ES cells. Upon differentiation, telomeric H3.3S31P signal decreases, accompanied by increased association of heterochromatin repressive marks and decreased micrococcal nuclease sensitivity at the telomeres. H3.3 is recruited to the telomeres at late S/G2 phase, coinciding with telomere replication and processing. RNAi-depletion of H3.3 induces telomere-dysfunction phenotype, providing evidence for a role of H3.3 in the regulation of telomere chromatin integrity in ES cells. The distinctive changes in H3.3 distribution suggests the existence of a unique and functionally essential telomere chromatin in ES cells that undergoes dynamic differentiation-dependent remodeling during the process of differentiation.",

author = "Wong, {Lee H} and Hua Ren and Williams, {Evan J} and McGhie, {James Derrick Robert} and Soyeon Ahn and Sim, {Marcus L J} and Angela Tam and Elizabeth Earle and Anderson, {Melissa A} and Mann, {Jeffrey R} and Andy Choo",

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doi = "10.1101/gr.084947.108",

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journal = "Genome Research",

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T1 - Histone H3.3 incorporation provides a unique and functionally essential telomeric chromatin in embryonic stem cells

AU - Wong, Lee H

AU - Ren, Hua

AU - Williams, Evan J

AU - McGhie, James Derrick Robert

AU - Ahn, Soyeon

AU - Sim, Marcus L J

AU - Tam, Angela

AU - Earle, Elizabeth

AU - Anderson, Melissa A

AU - Mann, Jeffrey R

AU - Choo, Andy

PY - 2009

Y1 - 2009

N2 - Little is known about the telomere chromatin dynamics of embryonic stem (ES) cell. Here, we demonstrate localization of histone H3.3 at interphase telomeres and enrichment of Ser31-phosphorylated H3.3 at metaphase telomeres in pluripotent mouse ES cells. Upon differentiation, telomeric H3.3S31P signal decreases, accompanied by increased association of heterochromatin repressive marks and decreased micrococcal nuclease sensitivity at the telomeres. H3.3 is recruited to the telomeres at late S/G2 phase, coinciding with telomere replication and processing. RNAi-depletion of H3.3 induces telomere-dysfunction phenotype, providing evidence for a role of H3.3 in the regulation of telomere chromatin integrity in ES cells. The distinctive changes in H3.3 distribution suggests the existence of a unique and functionally essential telomere chromatin in ES cells that undergoes dynamic differentiation-dependent remodeling during the process of differentiation.

AB - Little is known about the telomere chromatin dynamics of embryonic stem (ES) cell. Here, we demonstrate localization of histone H3.3 at interphase telomeres and enrichment of Ser31-phosphorylated H3.3 at metaphase telomeres in pluripotent mouse ES cells. Upon differentiation, telomeric H3.3S31P signal decreases, accompanied by increased association of heterochromatin repressive marks and decreased micrococcal nuclease sensitivity at the telomeres. H3.3 is recruited to the telomeres at late S/G2 phase, coinciding with telomere replication and processing. RNAi-depletion of H3.3 induces telomere-dysfunction phenotype, providing evidence for a role of H3.3 in the regulation of telomere chromatin integrity in ES cells. The distinctive changes in H3.3 distribution suggests the existence of a unique and functionally essential telomere chromatin in ES cells that undergoes dynamic differentiation-dependent remodeling during the process of differentiation.

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DO - 10.1101/gr.084947.108

M3 - Article

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VL - 19

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JO - Genome Research

JF - Genome Research

IS - 3

ER -

Histone H3.3 incorporation provides a unique and functionally essential telomeric chromatin in embryonic stem cells

Abstract

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