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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
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Heterochromatin revisited 总被引:10,自引:0,他引:10
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Domains of Heterochromatin Protein 1 Required for Drosophila melanogaster Heterochromatin Spreading
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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
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A key step in cellular senescence is the packaging of proliferation-promoting genes into repressive chromatin or heterochromatin. Recent work has described a novel histone component and mode of assembly of this senescence-associated heterochromatin. 相似文献
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Heterochromatin recognition with fluorochromes 总被引:2,自引:2,他引:0
Canio G. Vosa 《Chromosoma》1970,30(3):366-372
Some types of acridine derivative and especially Quinacrine dihydrochloride and its mustard may be successfully used as chromosome marker and to investigate the chemical differentiation of euchromatin and heterochromatin. — There are at least four main types of heterochromatin, showing all possible combinations of positive and negative cold effect starvation (St. + or St. -) and enhanced or reduced fluorescence (Fl. + or Fl. -). —The relationship between the four different classes of heterochromatin is not yet clear. 相似文献
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Dillon N 《Biology of the cell / under the auspices of the European Cell Biology Organization》2004,96(8):631-637
Although heterochromatin has long been used as a model for studying chromatin condensation and heritable gene silencing, it is only relatively recently that detailed information has become available on the mechanisms that underlie its structure. Current evidence suggests that these operate on at least three different levels. A regular nucleosome array may facilitate packaging of the chromatin into a highly condensed configuration. Methylation of histone H3 lysine 9 and lysine 27 generates heterochromatin marks that are recognised through binding of heterochromatin proteins such as HP1. Finally, very recent studies using genetic and biochemical approaches have indicated that the RNAi machinery plays an important role in the formation of heterochromatin. 相似文献
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Histone phosphorylation and nuclear structure have been compared in cultured cell lines of two related species of deer mice, Peromyscus crinitus and Peromyscus eremicus, which differ greatly in their heterochromatin contents but which contain essentially the same euchromatin content. Flow microfluorometry measurements indicated that P. eremicus contained 36% more DNA than did P. crinitus, and C-band chromosome staining indicated that the extra DNA of P. eremicus existed as constitutive heterochromatin. Two striking differences in interphase nuclear structure were observed by electron microscopy. Peromyscus crinitus nuclei contained small clumps of heterochromatin and a loose, amorphous nucleolus, while P. eremicus nuclei contained large, dense clumps of heterochromatin and a densely structured, well defined, nucleolonema form of nucleolus. Incorporation of 32PO4 into histones indicated that the steady-state phosphorylation of H1 was identical in P. crinitus and P. eremicus cells. In contrast, the phosphorylation rate of H2a was 58% greater in the highly heterochromatic chromatin of P. eremicus cells than in the lesser heterochromatic chromatin of P. crinitus cells, suggesting an involvement of H2a phosphorylation in heterochromatin structure. It is suggested that the three histone phosphorylations related to cell growth (H1, H2a, and H3) may be associated with different levels of chromatin organization: H1 interphase phosphorylation with some submicroscopic (molecular) level of organization, H2a phosphorylation with a higher level of chromatin organization found in heterochromatin, and H3 and H1 superphosphorylation with the highest level of chromatin organization observed in condensed chromosomes. 相似文献
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Heterochromatin and chromosome aberrations 总被引:2,自引:0,他引:2
The chromosome breaking effect of mitomycin C, methyl methanesulfonate, maleic hydrazide, 8-ethoxycaffeine and gamma rays on the primary root meristematic cells of Nigella damascena was studied. All the agents tested except 8-ethoxycaffeine, produced relatively fewer aberrations, when compared to Vicia faba cells, though both the species have nearly similar total chromosomal length. Test for the presence of heterochromatin in Nigella gave negative results and it is interpreted that the observed differences between Vicia and Nigella are due to the presence and absence of heterochromatin in their chromosome complements respectively. The role of heterochromatin in the production of chromosome aberrations and its significance in evolution are briefly discussed. 相似文献
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Verreault A 《Médecine sciences : M/S》2003,19(12):1181-1182
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Heterochromatin: silence is golden 总被引:14,自引:0,他引:14
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C. Barigozzi G. Badaracco P. Plevani L. Baratelli S. Profeta E. Ginelli R. Meneveri 《Chromosoma》1984,90(5):332-337
A bisexual species of the genus Artemia (Crustacea, Phyllopoda), Artemia franciscana Barigozzi of San Francisco Bay and a parthenogenetic population of Artemia sp. of Tsing-Tao (China), both with 42 chromosomes, were compared with respect to the microscopic structure of the interphase larval nucleus, the microscopical structure of the prophase chromosomes and the DNA structure. — Artemia franciscana exhibits several chromocenters in the resting nucleus, heterochromatic blocks located at the end of the prophase chromosomes, and a large amount of repetitive DNA (Alu I 110-bp fragments). The other Artemia sp. lacks chromocenters, heterochromatic blocks in the chromosomes, and the Alu I DNA. The two populations thus differ by a remarkable amount of repetitive DNA.The authors dedicate this paper to Professor Hans Bauer, on the occasion of his 80th birthday 相似文献
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Heterochromatin variation in Cryptobothrus chrysophorus 总被引:2,自引:0,他引:2
Northern and southern races of the Australian grasshopper Cryptobothrus chrysophorus share the same diploid chromosome number (2n=23, 24). The northern race is differentiated from the southern by fixed extra blocks of heterochromatin located distally on five of the six medium pairs of autosomes (M4, 5, 6, 8 and 9). The megameric M7 pair, which is completely heterochromatic in both races, is also frequently larger in the northern race. Additionally, while there is considerable polymorphism for the presence of supernumerary heterochromatic segments on the two smallest autosome pairs (S10, 11) in both races, the precise character of this polymorphism is strikingly different between them. That found in the north is both more extensive and more variable. An analysis of the patterns of C-banding obtained in neuroblast c-mitoses indicates even more variation within and between races than was anticipated from the patterns of heteropycnosis seen at first prophase of male meiosis. Thus, while the distal blocks on the M4, 6, 8 and 9 elements in the northern race invariably C-band those of the M5 never do. On the other hand polymorphisms for C-bands on the M5, 6, 8 and 9 are seen in some populations of the southern race but in regions which are not visibly heteropycnotic at meiosis. Polymorphisms for the pattern of C-banding also occur in the northern race populations in the M4, 6, 8 and 9 elements and some of these are associated with clear length differences in the chromosomes concerned. Others involve differences in the expression of the distal C-bands in M8 and 9 which vary from dark to intermediate. The supernumerary segments on the S10 and 11 pairs are especially variable in respect of their C-banding properties. Some are entirely C-banded, some show no C-banding whatsoever and some are composed of both banded and unhanded regions. Banding is again most pronounced, however, in the northern race. Finally the character of the megameric M7 is strikingly different in the two races not only in respect of its size, which is sometimes larger than that of the south, but also in respect of the extent of C-banding which is always more complex in the northern form irrespective of its size. 相似文献
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The Heterochromatin Protein 1 family 总被引:6,自引:0,他引:6