共查询到20条相似文献,搜索用时 15 毫秒
1.
2.
Heterochromatin 总被引:8,自引:0,他引:8
Hennig W 《Chromosoma》1999,108(1):1-9
The properties of heterochromatin are reconsidered in the context of our present understanding of gene silencing, telomeric
and centromeric properties, position-effect variegation and X-chromosome inactivation. It is proposed that the chromatin in
heterochromatic chromosomal regions is generally similar in its molecular composition to that in silenced chromosomal regions.
Heterochromatic appearance hence reflects not a particular quality of the respective chromosomal regions but only a specific
kind of chromatin packaging comparable to that required for the inactivation of genes. This packaging may be initiated by
particular signals in the DNA but can be propagated over more extended chromosomal regions by the formation of multiprotein
complexes that interact with histones and possibly cell-specific additional components (RNA or proteins) that determine the
status of the chromosome in a particular cell type.
Received: 15 November 1998 / Accepted: 8 December 1998 相似文献
3.
4.
Verreault A 《Médecine sciences : M/S》2003,19(12):1181-1182
5.
Heterochromatin: silence is golden 总被引:14,自引:0,他引:14
6.
7.
Heterochromatin revisited 总被引:10,自引:0,他引:10
8.
9.
10.
Mutation of the multi-KH domain protein DPP1, which has single-stranded nucleic acid binding activity, suppresses heterochromatin-mediated silencing in Drosophila; it also disrupts the modification of histone H3 at lysine 9, and association of heterochromatin protein 1 on the heterochromatic regions, suggesting a role for DDP1 in heterochromatin formation. 相似文献
11.
12.
《Cell cycle (Georgetown, Tex.)》2013,12(6):572-574
Considerable evidence connects heterochromatin or silenced chromatin with the Origin Recognition Complex (ORC) which is needed for initiation of DNA replication.1-7 In this review we consider biological forces that might be served by this connection. The prevailing view in the literature is that ORC recruits heterochromatin. This seems paradoxical because a replication initiator, ORC, would be recruiting factors which seem to oppose replication by forming inaccessible chromatin structures. Here we suggest a different view, that heterochromatin recruits ORC to facilitate replication of hard-to-replicate heterochromatic regions. We consider how existing data can be reconciled with this viewpoint, and we consider the biological predictions that arise from this perspective. 相似文献
13.
Su TT 《Current biology : CB》2010,20(23):R1018-R1020
14.
15.
16.
17.
18.
Domains of Heterochromatin Protein 1 Required for Drosophila melanogaster Heterochromatin Spreading 下载免费PDF全文
Karrie A. Hines Diane E. Cryderman Kaitlin M. Flannery Hongbo Yang Michael W. Vitalini Tulle Hazelrigg Craig A. Mizzen Lori L. Wallrath 《Genetics》2009,182(4):967-977
Centric regions of eukaryotic genomes are packaged into heterochromatin, which possesses the ability to spread along the chromosome and silence gene expression. The process of spreading has been challenging to study at the molecular level due to repetitious sequences within centric regions. A heterochromatin protein 1 (HP1) tethering system was developed that generates “ectopic heterochromatin” at sites within euchromatic regions of the Drosophila melanogaster genome. Using this system, we show that HP1 dimerization and the PxVxL interaction platform formed by dimerization of the HP1 chromo shadow domain are necessary for spreading to a downstream reporter gene located 3.7 kb away. Surprisingly, either the HP1 chromo domain or the chromo shadow domain alone is sufficient for spreading and silencing at a downstream reporter gene located 1.9 kb away. Spreading is dependent on at least two H3K9 methyltransferases, with SU(VAR)3-9 playing a greater role at the 3.7-kb reporter and dSETDB1 predominately acting at the 1.9 kb reporter. These data support a model whereby HP1 takes part in multiple mechanisms of silencing and spreading.HETEROCHROMATIN protein 1 (HP1) was identified in Drosophila as a nonhistone chromosomal protein enriched in centric heterochromatin (James and Elgin 1986; James et al. 1989). On polytene chromosomes, HP1 localizes near centromeres and telomeres, along the fourth chromosome and at ∼200 sites within the euchromatic arms (James et al. 1989; Fanti et al. 2003). Heterochromatin has the ability to “spread,” or propagate in cis, along the chromosome (Weiler and Wakimoto 1995). Spreading is observed when a chromosomal rearrangement places a euchromatic domain next to a heterochromatic domain. Cytologically, spreading is visualized as densely compact chromatin that emanates from the chromocenter, the structure formed by the fusion of centromeres, and extends into the banded regions of polytene chromosomes (Belyaeva and Zhimulev 1991). Euchromatic genes brought into juxtaposition with heterochromatin by chromosomal rearrangements exhibit gene silencing, termed position effect variegation (PEV) (Weiler and Wakimoto 1995). Mutations in Su(var)2-5, the gene encoding HP1, suppress silencing, suggesting HP1 plays a key role in spreading (Eissenberg et al. 1990). The molecular processes of spreading are not well understood.Repetitive sequences within heterochromatin make it difficult to study spreading at the molecular level. In addition, specific repetitive elements are thought to function as initiation sites for heterochromatin formation (Sun et al. 2004; Haynes et al. 2006), making it challenging to separate initiation from spreading. To overcome these problems, we generated a system that nucleates small domains (<20 kb) of repressive chromatin that share many properties with centric heterochromatin. Here we refer to these as ectopic heterochromatin domains. These domains are generated by expressing a fusion protein, consisting of the DNA binding domain of the Escherichia coli lac repressor (LacI) fused to HP1, in stocks possessing lac operator (lacO) repeats upstream of a reporter gene cassette (Danzer and Wallrath 2004). LacI-HP1 associates with the lacO repeats and causes silencing of the adjacent reporter genes. Silencing correlates with alterations in chromatin structure that include the generation of regular nucleosome arrays similar to those observed in centric heterochromatin (Sun et al. 2001; Danzer and Wallrath 2004). Chromatin immunoprecipitation (ChIP) experiments demonstrated that HP1 spreads bidirectionally, 5–10 kb from the lacO repeats, encompassing the reporter genes (Danzer and Wallrath 2004). Thus, HP1 is sufficient to nucleate small heterochromatin-like domains at genomic locations devoid of repetitious sequences, allowing for molecular studies of spreading.HP1 contains an amino terminal chromo domain (CD) and a carboxy chromo shadow domain (CSD), separated by a flexible hinge (Li et al. 2002). The CD forms a hydrophobic pocket implicated in chromosomal association through binding to di- and trimethylated lysine 9 of histone H3 (H3K9me2 and me3, respectively), an epigenetic mark generated by the histone methyltransferases (HMT) SU(VAR)3-9 and dSETDB1 (also known as Egg) (Jacobs et al. 2001; Schotta et al. 2002; Schultz et al. 2002; Ebert et al. 2004; Clough et al. 2007; Seum et al. 2007; Tzeng et al. 2007). Association with methylated H3 is one mechanism of HP1 chromosome association; however, other mechanisms involving interactions with DNA and/or partner proteins likely exist (Fanti et al. 1998; Li et al. 2002; Cryderman et al. 2005). In Drosophila HP1, a single amino acid substitution within the CD (V26M) is present in the Su(var)2-502 allele; flies heterozygous for this allele show suppression of gene silencing by heterochromatin (Eissenberg et al. 1990). Furthermore, flies trans-heterozygous for Su(var)2-502 and a null allele of Su(var)2-5 show dramatic reduction of HP1 near centromeres and do not survive past the third larval stage (Fanti et al. 1998). Consistent with these observations, structural studies show that V26 plays a critical role in forming the hydrophobic pocket of the CD that binds to H3K9me (Jacobs et al. 2001).The HP1 CSD dimerizes and mediates interactions with a variety of nuclear proteins (Cowieson et al. 2000; Yamamoto and Sonoda 2003; Thiru et al. 2004). CSD dimerization sets up an interaction platform for the binding of proteins possessing a penta-peptide motif, PxVxL (where x represents any amino acid) (Thiru et al. 2004; Lechner et al. 2005). Amino acid substitutions within HP1 have been identified that disrupt dimerization, and interaction with PxVxL proteins (Lechner et al. 2000; Thiru et al. 2004). For example, a single amino acid substitution within the CSD (I161E) disrupts dimerization of mouse HP1beta (Brasher et al. 2000). The lack of dimerization also caused the loss of interactions with nuclear factors containing PxVxL motifs and non-PxVxL partners (Yamamoto and Sonoda 2003; Lechner et al. 2005). In contrast, a single amino acid substitution elsewhere in the CSD (W170A) of mouse HP1beta does not prevent dimerization, but disrupts the interaction with PxVxL partner proteins (Brasher et al. 2000). Therefore, the requirement for HP1 dimerization and binding to the PxVxL proteins can be functionally separated. Here, we investigate effects of HP1 domain deletions and amino acid substitutions on HP1 localization, partner protein interactions, and heterochromatin spreading. 相似文献
19.