Histone H3.3 incorporation provides a unique and functionally essential telomeric chromatin in embryonic stem cells.
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.
Wong
Lee H
LH
Chromosome and Chromatin Research Laboratory, Murdoch Childrens Research Institute, Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Parkville 3052, Victoria, Australia. lee.wong@mcri.edu.au
Ren
Hua
H
Williams
Evan
E
McGhie
James
J
Ahn
Soyeon
S
Sim
Marcus
M
Tam
Angela
A
Earle
Elizabeth
E
Anderson
Melissa A
MA
Mann
Jeffrey
J
Choo
K H Andy
KH
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D002675:Child, Preschool; D002843:Chromatin / Q000378:metabolism / Q000502:physiology*; D004261:DNA Replication / Q000235:genetics / Q000502:physiology; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D006657:Histones / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D007399:Interphase / Q000235:genetics / Q000502:physiology; D051379:Mice; D008938:Mitosis / Q000235:genetics / Q000502:physiology; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D006656:Protamine Kinase / Q000378:metabolism; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D016615:Telomere / Q000378:metabolism*
D002843:Chromatin; D006657:Histones; D006656:Protamine Kinase; D017346:Protein Serine-Threonine Kinases