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

被引:135
作者
Wong, Lee H. [1 ]
Ren, Hua [1 ]
Williams, Evan [1 ]
McGhie, James [1 ]
Ahn, Soyeon [1 ]
Sim, Marcus [1 ]
Tam, Angela [1 ]
Earle, Elizabeth [1 ]
Anderson, Melissa A. [1 ]
Mann, Jeffrey [2 ]
Choo, K. H. Andy [1 ]
机构
[1] Univ Melbourne, Chromosome & Chromatin Res Lab, Murdoch Childrens Res Inst, Dept Paediat,Royal Childrens Hosp, Parkville, Vic 3052, Australia
[2] Univ Melbourne, Stem Cell Epigenet Res Lab, Murdoch Childrens Res Inst, Dept Paediat,Royal Childrens Hosp, Parkville, Vic 3052, Australia
基金
英国医学研究理事会;
关键词
EPIGENETIC REGULATION; ACTIVE CHROMATIN; MAMMALIAN-CELLS; VARIANT H3.3; DNA; METHYLTRANSFERASES; RECOMBINATION; CHROMOSOMES; LENGTH;
D O I
10.1101/gr.084947.108
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:404 / 414
页数:11
相关论文
共 19 条
[1]   The histone variant H3.3 marks active chromatin by replication-independent nucleosome assembly [J].
Ahmad, K ;
Henikoff, S .
MOLECULAR CELL, 2002, 9 (06) :1191-1200
[2]   Chromatin signatures of pluripotent cell lines [J].
Azuara, V ;
Perry, P ;
Sauer, S ;
Spivakov, M ;
Jorgensen, HF ;
John, RM ;
Gouti, M ;
Casanova, M ;
Warnes, G ;
Merkenschlager, M ;
Fisher, AG .
NATURE CELL BIOLOGY, 2006, 8 (05) :532-U189
[3]   The epigenetic regulation of mammalian telomeres [J].
Blasco, Maria A. .
NATURE REVIEWS GENETICS, 2007, 8 (04) :299-309
[4]   Telomere measurement by quantitative PCR [J].
Cawthon, RM .
NUCLEIC ACIDS RESEARCH, 2002, 30 (10) :e47
[5]   Telomeric DNA in ALT cells is characterized by free telomeric circles and heterogeneous t-loops [J].
Cesare, AJ ;
Griffith, JD .
MOLECULAR AND CELLULAR BIOLOGY, 2004, 24 (22) :9948-9957
[6]   Epigenetic regulation of telomere length in mammalian cells by the Suv39h1 and Suv39h2 histone methyltransferases [J].
García-Cao, M ;
O'Sullivan, R ;
Peters, AHFM ;
Jenuwein, T ;
Blasco, MA .
NATURE GENETICS, 2004, 36 (01) :94-99
[7]   DNA methylation affects nuclear organization, histone modifications, and blinker histone binding but not chromatin compaction [J].
Gilbert, Nick ;
Thomson, Inga ;
Boyle, Shelagh ;
Allan, James ;
Ramsahoye, Bernard ;
Bickmore, Wendy A. .
JOURNAL OF CELL BIOLOGY, 2007, 177 (03) :401-411
[8]   DNA methyltransferases control telomere length and telomere recombination in mammalian cells [J].
Gonzalo, S ;
Jaco, I ;
Fraga, MF ;
Chen, TP ;
Li, E ;
Esteller, M ;
Blasco, MA .
NATURE CELL BIOLOGY, 2006, 8 (04) :416-U66
[9]   Serine 31 phosphorylation of histone variant H3.3 is specific to regions bordering centromeres in metaphase chromosomes [J].
Hake, SB ;
Garcia, BA ;
Kauer, M ;
Baker, SP ;
Shabanowitz, J ;
Hunt, DF ;
Allis, CD .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (18) :6344-6349
[10]   POT1 protects telomeres from a transient DNA damage response and determines how human chromosomes end [J].
Hockemeyer, D ;
Sfeir, AJ ;
Shay, JW ;
Wright, WE ;
de Lange, T .
EMBO JOURNAL, 2005, 24 (14) :2667-2678