Lsh, a guardian of heterochromatin at repeat elements

被引:51
作者
Muegge, K [1 ]
机构
[1] NCI, Lab Canc Prevent, SAIC, FCRDC, Frederick, MD 21701 USA
关键词
chromatin; methylation; Lsh; DNA repeats;
D O I
10.1139/O05-119
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
Lymphoid-specific helicase (Lsh) is a crucial factor for normal embryonic development; targeted deletion of Lsh is lethal. Lsh belongs to a family of chromatin-remodeling proteins and is closely associated with pericentromeric heterochromatin. Lsh deficiency leads to abnormal heterochromatin organization, with a loss of DNA methylation, and an altered pattern of histone-tail acetylation and methylation. As a functional consequence of perturbed heterochromatin, aberrant reactivation of parasitic retroviral elements in the genome and abnormal mitosis with amplified centrosomes and genomic instability were observed. Thus, Lsh is a major epigenetic regulator crucial for normal heterochromatin structure and function.
引用
收藏
页码:548 / 554
页数:7
相关论文
共 39 条
[1]   DNA methylation patterns and epigenetic memory [J].
Bird, A .
GENES & DEVELOPMENT, 2002, 16 (01) :6-21
[2]  
BIRD J, 2003, CLIN GENET, V64, P83
[3]  
BIRD S, 2002, CANCER CELL, V1, P299
[4]   A Brg1 null mutation in the mouse reveals functional differences among mammalian SWI/SNF complexes [J].
Bultman, S ;
Gebuhr, T ;
Yee, D ;
La Mantia, C ;
Nicholson, J ;
Gilliam, A ;
Randazzo, F ;
Metzger, D ;
Chambon, P ;
Crabtree, G ;
Magnuson, T .
MOLECULAR CELL, 2000, 6 (06) :1287-1295
[5]   Lsh, a member of the SNF2 family, is required for genome-wide methylation [J].
Dennis, K ;
Fan, T ;
Geiman, T ;
Yan, QS ;
Muegge, K .
GENES & DEVELOPMENT, 2001, 15 (22) :2940-2944
[6]   EVOLUTION OF THE SNF2 FAMILY OF PROTEINS - SUBFAMILIES WITH DISTINCT SEQUENCES AND FUNCTIONS [J].
EISEN, JA ;
SWEDER, KS ;
HANAWALT, PC .
NUCLEIC ACIDS RESEARCH, 1995, 23 (14) :2715-2723
[7]   Heterochromatin: stable and unstable invasions at home and abroad [J].
Fahrner, JA ;
Baylin, SB .
GENES & DEVELOPMENT, 2003, 17 (15) :1805-1812
[8]   DNA hypomethylation perturbs the function and survival of CNS neurons in postnatal animals [J].
Fan, GP ;
Beard, C ;
Chen, RZ ;
Csankovszki, G ;
Sun, Y ;
Siniaia, M ;
Biniszkiewicz, D ;
Bates, B ;
Lee, PP ;
Kühn, R ;
Trumpp, A ;
Poon, CS ;
Wilson, CB ;
Jaenisch, R .
JOURNAL OF NEUROSCIENCE, 2001, 21 (03) :788-797
[9]   Lsh controls silencing of the imprinted Cdkn1c gene [J].
Fan, T ;
Hagan, JP ;
Kozlov, SV ;
Stewart, CL ;
Muegge, K .
DEVELOPMENT, 2005, 132 (04) :635-644
[10]  
Fan T, 2003, CANCER RES, V63, P4677