The core of the polycomb repressive complex is compositionally and functionally conserved in flies and humans

被引:318
作者
Levine, SS
Weiss, A
Erdjument-Bromage, H
Shao, ZH
Tempst, P
Kingston, RE [1 ]
机构
[1] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA
[2] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA
[3] Mem Sloan Kettering Canc Ctr, Program Mol Biol, New York, NY 10021 USA
关键词
D O I
10.1128/MCB.22.17.6070-6078.2002
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
The Polycomb group (PcG) genes are required to maintain homeotic genes in a silenced state during development in drosophila and mammals and are thought to form several distinct silencing complexes that maintain homeotic gene repression during development. Mutations in the PcG genes result in developmental defects and have been implicated in human cancer. Although some PcG protein domains are conserved between flies and humans, substantial regions of several PcG proteins are divergent and humans contain multiple versions of each PcG gene. To determine the effects of these changes on the composition and function of a PcG complex, we have purified a human Polycomb repressive complex from HeLa cells (hPRC-H) that contains homologues of PcG proteins found in drosophila embryonic PRC1 (dPRC1). hPRC-H was found to have fewer components than dPRC1, retaining the PcG core proteins of dPRC1 but lacking most non-PcG proteins. Preparations of hPRC-H contained either two or three different homologues of most of the core PcG proteins, including a new Ph homologue we have named HPH3. Despite differences in composition, dPRC1 and hPRC-H have similar functions: hPRC-H is able to efficiently block remodeling of nucleosomal arrays through a mechanism that does not block the ability of nucleases to access and cleave the arrays.
引用
收藏
页码:6070 / 6078
页数:9
相关论文
共 66 条
[1]  
Akasaka T, 1996, DEVELOPMENT, V122, P1513
[2]  
Akasaka T, 2001, DEVELOPMENT, V128, P1587
[3]   Identification of Bmi1-interacting proteins as constituents of a multimeric mammalian Polycomb complex [J].
Alkema, MJ ;
Bronk, M ;
Verhoeven, E ;
Otte, A ;
vantVeer, LT ;
Berns, A ;
vanLohuizen, M .
GENES & DEVELOPMENT, 1997, 11 (02) :226-240
[4]   HPC3 is a new human polycomb orthologue that interacts and associates with RING1 and Bmi1 and Has transcriptional repression properties [J].
Bárdos, JI ;
Saurin, AJ ;
Tissot, C ;
Duprez, E ;
Freemont, PS .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (37) :28785-28792
[5]   The human homolog of Sex comb on midleg (SCMH1) maps to chromosome 1p34 [J].
Berger, J ;
Kurahashi, H ;
Takihara, Y ;
Shimada, K ;
Brock, HW ;
Randazzo, F .
GENE, 1999, 237 (01) :185-191
[6]  
Beuchle D, 2001, DEVELOPMENT, V128, P993
[7]   A family of chromatin remodeling factors related to Williams syndrome transcription factor [J].
Bochar, DA ;
Savard, J ;
Wang, WD ;
Lafleur, DW ;
Moore, P ;
Côté, J ;
Shiekhattar, R .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (03) :1038-1043
[8]   General transcription factors bind promoters repressed by Polycomb group proteins [J].
Breiling, A ;
Turner, BM ;
Bianchi, ME ;
Orlando, V .
NATURE, 2001, 412 (6847) :651-655
[9]   DROSOPHILA GENES POSTERIOR SEX COMBS AND SUPPRESSOR 2 OF ZESTE ENCODE PROTEINS WITH HOMOLOGY TO THE MURINE BMI-1 ONCOGENE [J].
BRUNK, BP ;
MARTIN, EC ;
ADLER, PN .
NATURE, 1991, 353 (6342) :351-353
[10]   TRANSCRIPTIONAL REPRESSION BY DROSOPHILA AND MAMMALIAN POLYCOMB GROUP PROTEINS IN TRANSFECTED MAMMALIAN-CELLS [J].
BUNKER, CA ;
KINGSTON, RE .
MOLECULAR AND CELLULAR BIOLOGY, 1994, 14 (03) :1721-1732