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A ‘higher order’ of telomere regulation: telomere) I3 ^+ ~4 u! B' }8 a9 T; z/ O$ S# T$ ~
heterochromatin and telomeric RNAs, @* q. m1 B) F$ N$ R, a
: V( m4 v8 L1 x& x7 ], F9 q7 [
EMBO 2009
$ e2 g; S! u s7 o. F9 \; g, `Protection of chromosome ends from DNA repair and1 V/ Q/ L' p* V/ P3 Y- Q$ o( X: p. Y
degradation activities is mediated by specialized protein: |, o' ^1 w& @7 V0 m
complexes bound to telomere repeats. Recently, it has
1 p: D }9 y# I: p8 Vbecome apparent that epigenetic regulation of the( g6 L$ J5 ^( I! I5 f
telomeric chromatin template critically impacts on
, }0 {, ?: B( c# W/ M. ttelomere function and telomere-length homeostasis from9 N8 q0 m$ C! y! Y. P8 d9 p& k
yeast to man. Across all species, telomeric repeats as well1 ~# o2 x: a" L" i
as the adjacent subtelomeric regions carry features of+ Z1 u, [* L5 P$ [" H
repressive chromatin. Disruption of this silent chromatin0 x) c1 u$ |* v# j3 J% x9 G* o6 Y
environment results in loss of telomere-length control/ }/ } N8 Z; k9 {. e8 V" S
and increased telomere recombination. In turn, progressive
, r. x9 j5 K+ X9 x4 N' ]6 S5 S# i$ G& Ztelomere loss reduces chromatin compaction at" |6 o# K) d |/ |& h( O
telomeric and subtelomeric domains. The recent discoveries
, {+ `8 b; _- U% P% zof telomere chromatin regulation during early mammalian: d: y d* ~# F8 c3 V
development, as well as during nuclear
: x! `; o t& [+ C% S) Breprogramming, further highlights a central role of telomere
/ Z/ ~# ~) H; {6 L2 dchromatin changes in ontogenesis. In addition,, V; W- d* v* `5 ~/ \, @+ J
telomeres were recently shown to generate long, noncoding4 Y* ]; S- j8 S( @ h6 p5 N2 N
RNAs that remain associated to telomeric chromatin# J" U8 {$ ]7 p7 t% Y5 v; p2 S1 D
and will provide new insights into the regulation of+ F' }- ]- l3 s' K! E0 @
telomere length and telomere chromatin. In this review,+ M4 O0 x& ~* y7 L3 ~
we will discuss the epigenetic regulation of telomeres1 _: ~( b% [( B' O/ H2 D/ h% K8 B
across species, with special emphasis on mammalian/ q: @' V/ p* F C* l/ u
telomeres. We will also discuss the links between
; o1 }+ R" O* }- F, Q9 J6 E; j, q+ e+ sepigenetic alterations at mammalian telomeres and$ j) J2 J$ y: c5 |* `0 E& J1 ^
telomere-associated diseases. |
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发表于 2010-4-7 10:11
发表于 2010-4-20 16:04
