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At least 19 recordsLinked to original sources
PubMed1982

Asynchronous replication of constitutive heterochromatin on X chromosomes in female Mus dunni. Possible influence of facultative heterochromatin on the adjacent constitutive heterochromatin.

Euchromatin DNA of one X chromosome in mammalian females, which becomes facultatively heterochromatinized, is known to replicate asynchronously late in S phase compared to its active homologue. In the females of a pygmy mouse species Mus dunni, which has prominent segment of constitutive heterochromatin as the short arm of its submetacentric X chromosome, we have observed asynchronous replication of c-heterochromatin arm as well, predominant number of cells showing the segment associated with the facultatively heterochromatic X to be terminating later. The preferential later termination of replication of the c-heterochromatic arm on the "lyonized X" appears to be due to the influence of facultative heterochromatin on the adjacent constitutive heterochromatin.

Animals↗
PubMed2002

Fission yeast CENP-B homologs nucleate centromeric heterochromatin by promoting heterochromatin-specific histone tail modifications.

Heterochromatin is a functionally important chromosomal component, especially at centromeres. In fission yeast, conserved heterochromatin-specific modifications of the histone H3 tail, involving deacetylation of Lys 9 and Lys 14 and subsequent methylation of Lys 9, promote the recruitment of a heterochromatin protein, Swi6, a homolog of the Drosophila heterochromatin protein 1. However, the primary determinants of the positioning of heterochromatin are still unclear. The fission yeast proteins Abp1, Cbh1, and Cbh2 are homologs of the human protein CENP-B that bind to centromeric alpha-satellite DNA and associate with centromeric heterochromatin. We show that the CENP-B homologs are functionally redundant at centromeres, and that Abp1 binds specifically to centromeric heterochromatin. In the absence of Abp1 or Cbh1, the centromeric association of Swi6 is diminished, resulting in a decrease in silencing of the region. CENP-B-homolog double disruptants show a synergistic reduction of Swi6 at centromeric heterochromatin, indicating that the three proteins are functionally redundant in the recruitment of Swi6. Furthermore, using chromatin immunoprecipitation assays, we show that disruption of CENP-B homologs causes a decrease in heterochromatin-specific modifications of histone H3. These results indicate that the CENP-B homologs act as site-specific nucleation factors for the formation of centromeric heterochromatin by heterochromatin-specific modifications of histone tails.

Autoantigens↗
PubMed2003

Association of Lsh, a regulator of DNA methylation, with pericentromeric heterochromatin is dependent on intact heterochromatin.

The eukaryotic genome is packaged into distinct domains of transcriptionally active euchromatin and silent heterochromatin. A hallmark of mammalian heterochromatin is CpG methylation. Lsh, a member of the SNF2 family, is a major regulator of DNA methylation in mice and thus crucial for normal heterochromatin formation. In order to define the molecular function of Lsh, we examined its cellular localization and its association with chromatin. Our studies demonstrate that Lsh is an exclusively nuclear protein, and we define a nuclear localization domain within the N-terminal portion of Lsh. Lsh strongly associates with chromatin and requires the internal and C-terminal regions for this interaction. Lsh accumulates at pericentromeric heterochromatin, suggesting a direct role for Lsh in the methylation of centromeric DNA sequences and the formation of heterochromatin. In search of a signal that is responsible for Lsh recruitment to pericentromeric heterochromatin, we found that histone tail modifications were critical. Prolonged treatment with histone deacetylase inhibitors has been reported to disrupt higher-order heterochromatin organization, and this was accompanied by dissociation of Lsh from pericentromeric heterochromatin. These results are consistent with a model in which Lsh is recruited by intact heterochromatin structure and then assists in maintaining heterochromatin organization by establishing CpG methylation patterns.

Animals↗
PubMed2003

Components of a pathway maintaining histone modification and heterochromatin protein 1 binding at the pericentric heterochromatin in Mammalian cells.

Heterochromatin is a higher order chromatin structure that is important for transcriptional silencing, chromosome segregation, and genome stability. The establishment and maintenance of heterochromatin is regulated not only by genetic elements but also by epigenetic elements that include histone tail modification (e.g. acetylation and methylation) and DNA methylation. Here we show that the p33ING1-Sin3-HDAC complex as well as DNA methyltransferase 1 (DNMT1) and DNMT1-associated protein 1 (DMAP1) are components of a pathway required for maintaining proper histone modification and heterochromatin protein 1 binding at the pericentric heterochromatin. p33ING1 and DMAP1 interact physically and co-localize to heterochromatin in the late S phase, and both are required for heterochromatin protein 1 binding to heterochromatin. Although the p33ING1-Sin3-HDAC and DMAP1-DNMT1 complexes are recruited independently to pericentric heterochromatin regions, they are both required for deacetylation of histones and methylation of histone H3 at lysine 9. These data support a cooperative model for histone deacetylation, methylation, and DNA methylation in maintaining pericentric heterochromatin structure throughout cell divisions.

Chromobox Protein Homolog 5↗
PubMed1976

Fine structure of the heterochromatin of the kangaroo rat Dipidomys ordii, and examination of the possible role of actin and myosin in heterochromatin condensation.

Biochemical studies have suggested that some actin and myosin may be present in the nucleus. This raises the possibility that heterochromatin condensation might be the result of an actin-myosin rigour type complex. Since ATP dissociates actin and myosin, this possibility could be examined by determining the effect of ATP on heterochromatin condensation. Thin-section electron microscopy showed large amounts of condensed constitutive heterochromatin in the kidney nuclei and somewhat less in the liver nuclei of the kangaroo rat, Dipidomys ordii. Surprisingly, there were some nuclei in the brain which contained no condensed heterochromatin despite the fact that this genome is composed of 50% satellite DNA. Although washing kidney nuclei with solutions of 10 mM Tris-ATP caused marked decondensation of the heterochromatin, when they were washed with Mg-ATP the heterochromatin was more condensed than in the controls. This suggests the decondensation by Tris-ATP is due to its ability to chelate divalent cations and provides no support for condensation of heterochromatin being the result of myosin-actin interaction. Despite being decondensed, the chromatin fibres of heterochromatin were distinct from those of euchromatin. The heterochromatin formed rod-like 19-5 nm fibres, the euchromatin formed random coils of 11-0-nm fibres.

Actins↗
PubMed1997

An actin-related protein in Drosophila colocalizes with heterochromatin protein 1 in pericentric heterochromatin.

The actin-related proteins have been identified by virtue of their sequence similarity to actin. While their structures are thought to be closely homologous to actin, they exhibit a far greater range of functional diversity. We have localized the Drosophila actin-related protein, Arp4, to the nucleus. It is most abundant during embryogenesis but is expressed at all developmental stages. Within the nucleus Arp4 is primarily localized to the centric heterochromatin. Polytene chromosome spreads indicate it is also present at much lower levels in numerous euchromatic bands. The only other protein in Drosophila reported to be primarily localized to centric heterochromatin in polytene nuclei is heterochromatin protein 1 (HP1), which genetic evidence has linked to heterochromatin-mediated gene silencing and alterations in chromatin structure. The relationship between Arp4 and heterochromatin protein 1 (HP1) was investigated by labeling embryos and larval tissues with antibodies to Arp4 and HP1. Arp4 and HP1 exhibit almost superimposable heterochromatin localization patterns, remain associated with the heterochromatin throughout prepupal development, and exhibit similar changes in localization during the cell cycle. Polytene chromosome spreads indicate that the set of euchromatic bands labeled by each antibody overlap but are not identical. Arp4 and HP1 in parallel undergo several shifts in their nuclear localization patterns during embryogenesis, shifts that correlate with developmental changes in nuclear functions. The significance of their colocalization was further tested by examining nuclei that express mutant forms of HP1. In these nuclei the localization patterns of HP1 and Arp4 are altered in parallel fashion. The morphological, developmental and genetic data suggest that, like HP1, Arp4 may have a role in heterochromatin functions.

Actins↗
PubMed2005

A glue for heterochromatin maintenance: stable SUV39H1 binding to heterochromatin is reinforced by the SET domain.

Trimethylation of histone H3 lysine 9 and the subsequent binding of heterochromatin protein 1 (HP1) mediate the formation and maintenance of pericentromeric heterochromatin. Trimethylation of H3K9 is governed by the histone methyltransferase SUV39H1. Recent studies of HP1 dynamics revealed that HP1 is not a stable component of heterochromatin but is highly mobile (Cheutin, T., A.J. McNairn, T. Jenuwein, D.M. Gilbert, P.B. Singh, and T. Misteli. 2003. Science. 299:721-725; Festenstein, R., S.N. Pagakis, K. Hiragami, D. Lyon, A. Verreault, B. Sekkali, and D. Kioussis. 2003. Science. 299:719-721). Because the mechanism by which SUV39H1 is recruited to and interacts with heterochromatin is unknown, we studied the dynamic properties of SUV39H1 in living cells by using fluorescence recovery after photobleaching and fluorescence resonance energy transfer. Our results show that a substantial population of SUV39H1 is immobile at pericentromeric heterochromatin, suggesting that, in addition to its catalytic activity, SUV39H1 may also play a structural role at pericentromeric regions. Analysis of SUV39H1 deletion mutants indicated that the SET domain mediates this stable binding. Furthermore, our data suggest that the recruitment of SUV39H1 to heterochromatin is at least partly independent from that of HP1 and that HP1 transiently interacts with SUV39H1 at heterochromatin.

Animals↗
PubMed1994

[A cytogenetic study of the functions of the variable regions in human C heterochromatin. I. The effect of C heterochromatin on gene expression].

In our previous studies we have demonstrated that the degree of the growth retardation shows a positive correlation with the reduction of C heterochromatin in chromosomes 1, 9, and 16 in patients with embryopathies of unknown etiology and in children with trisomy 21. The investigation of C heterochromatin in these chromosomes in patients with obligate growth retardation and gene syndromes with a postulated Mendelian inheritance (Russell-Silver, Dubowitz etc.) has revealed a reduced C heterochromatin amount. No large C segments were seen in all of the 32 patients. Only 2 large C segments were found in 42 parents that were never inherited. The lowest amount of C heterochromatin was found in the most shortish fathers and mothers. The short stature of healthy parents in patients with the above mentioned syndromes is usually regarded as resulting from an incomplete mutant gene expression. The present results, when taken in conjunction with those of our previous study, enable us to suggest another interpretation: (i) the growth retardation in children with gene syndromes and low height of parents may be due to the reduction of C heterochromatin in chromosomes 1, 9, and 16, i.e. the mutant genes are not the only reason of the growth retardation; (ii) the obligatory growth retardation in the above syndromes can be explained by the fact that the expression of corresponding genes is possible only in genomes with a low C heterochromatin amount; (iii) the C heterochromatin in chromosomes 1, 9, and 16 influences on the number of mutant genes expression in man.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1998

Beta-heterochromatin in mammals: evidence from studies in Microtus agrestis based on the extensive accumulation of L1 and non-L1 retroposons in the heterochromatin.

The heterochromatin of Microtus agrestis contains two retroposons, one L1 and one non-L1, which were cloned and analyzed with respect to their structure and genomic organization. These sequences have accumulated in the heterochromatin and exhibit a complex interspersed organization of relatively recent origin. In contrast, the pericentromeric heterochromatin is composed of simple, repetitive, tandemly organized elements. From the underlying sequences, the dinucleotide frequencies, the sequence organization, and its transcriptional activity, the heterochromatin of M. agrestis strongly resembles the beta-heterochromatin first described by Heitz and well characterized in Drosophila. This is evidence that this class of heterochromatin, presumably with its own distinct physiological and functional role, is indeed also present in the mammalian genome.

Animals↗
PubMed1994

[A cytogenetic study of the functions of the variable regions in human C heterochromatin. III. The relationship between the amount of C heterochromatin and the occurrence of the fetal alcohol syndrome].

It has been shown elsewhere that in children with growth retardation and gene syndromes (Russell-Silver, Dubowitz etc.), and in healthy children with inherited short stature the total amount of C heterochromatin in chromosomes 1, 9, and 16 was reduced as compared to the control. A correlation between the C heterochromatin reduction and the intrauterine growth retardation was suggested. A study of C heterochromatin in patients with fetal alcohol syndrome has shown that the chromosome sets of all the 11 children examined are identical to those of the above-mentioned patients. This fact may indicate that a small amount of C heterochromatin may play the leading role in realization of the alcohol effect, since this C heterochromatin deficiency makes the early embryogenesis open to injury to external effects. A possible functional role of C heterochromatin in disturbances of the developmental homeostasis are discussed. These disturbances concern the growth retardation and the lack of resistance to the effect of external and internal factors.

Child↗
PubMed1994

Increased phosphorylation of HP1, a heterochromatin-associated protein of Drosophila, is correlated with heterochromatin assembly.

The heterochromatin-associated nonhistone chromosomal protein HP1 exerts dosage-dependent effects on the silencing of genes juxtaposed to pericentric heterochromatin in Drosophila melanogaster. Here, we report that HP1 is multiply phosphorylated in Drosophila tissue, predominantly at serine and threonine residues. Pulse-labeling studies of explanted Drosophila tissues suggest that phosphorylation is relatively rapid and that phosphate is incorporated into existing protein. Maternally synthesized HP1 is underphosphorylated. The appearance of more highly phosphorylated HP1 isoforms at 1.5-2 h of development coincides with the embryonic stage at which cytologically visible heterochromatin appears and HP1 concentrates in heterochromatin. The extent of HP1 phosphorylation is lower in polytene tissue, where heterochromatin is underrepresented. These results are consistent with a role for phosphorylation of HP1 in the assembly and maintenance of heterochromatin in Drosophila.

Amino Acid Sequence↗
PubMed1979

Studies in heterochromatin DNA: accessibility of late replicating heterochromatin DNA in chromatin to micrococcal nuclease digestion.

Heterochromatin DNA in cactus mouse (Peromyscus eremicus) replicates in the late S phase of cell cycle. A method of obtaining cells which contain DNA preferentially labeled at heterochromatic areas by a pulse-labeling of late replicating DNA is described. When the nuclei of P. eremicus cells containing radioactively labeled DNA in heterochromatin were digested with micrococcal nuclease and the resultant nucleosomal DNA was separated by gel electrophoresis, it was found that the repeat length of nucleosomal DNA in the heterochromatin DNA is not different from that of the bulk of the genomic DNA. Furthermore, there was no significant difference in the accessibility to digestion by micrococcal nuclease between the late replicating heterochromatin DNA and the total DNA under our digestion conditions. Two dimensional gel electrophoresis patterns of nucleosomal DNAs isolated from micrococcal nuclease digested nuclei from P. eremicus, P. collatus, and P. crinitus cells in culture were very similar. Cytogenetic data showed that these three species are different in heterochromatin but similar in euchromatin.

Animals↗
PubMed1977

Genetic dissection of heterochromatin in Drosophila: the role of basal X heterochromatin in meiotic sex chromosome behaviour.

We have examined the female meiotic behaviour of three X-chromosomes which have large deletions of the basal heterochromatin in Drosophila melanogaster. We find that most of this heterochromatin can be removed without substantially altering pairing and segregation of the two Xs. To compare the role of heterochromatin in male meiosis we have constructed individuals which carry two extra identical heterochromatic mini X chromosomes. These minis behave as univalents even though their heterochromatin is known to contain satellite DNA. We conclude therefore that this satellite DNA is not sufficient to allow effectively normal meiotic behaviour. In all other respects our results in the male extend and confirm Cooper's postulate that there exist specific pairing sites in the X heterochromatin. Thus we find no support in either female or male meiosis for the concenpt that satellite DNA is involved in meiotic chromosome pairing of either a chiasmate or an achiasmate kind.

Animals↗
PubMed2002

Heterochromatin protein 2 (HP2), a partner of HP1 in Drosophila heterochromatin.

Heterochromatin protein 1 (HP1), first discovered in Drosophila melanogaster, is a highly conserved chromosomal protein implicated in both heterochromatin formation and gene silencing. We report here characterization of an HP1-interacting protein, heterochromatin protein 2 (HP2), which codistributes with HP1 in the pericentric heterochromatin. HP2 is a large protein with two major isoforms of approximately 356 and 176 kDa. The smaller isoform is produced from an alternative splicing pattern in which two exons are skipped. Both isoforms contain the domain that interacts with HP1; the larger isoform contains two AT-hook motifs. Mutations recovered in HP2 act as dominant suppressors of position effect variegation, confirming a role in heterochromatin spreading and gene silencing.

AT Rich Sequence↗
PubMed1999

Phosphorylation of heterochromatin protein 1 by casein kinase II is required for efficient heterochromatin binding in Drosophila.

Heterochromatin-associated protein 1 (HP1) is a nonhistone chromosomal protein with a dose-dependent effect on heterochromatin mediated position-effect silencing. It is multiply phosphorylated in vivo. Hyperphosphorylation of HP1 is correlated with heterochromatin assembly. We report here that HP1 is phosphorylated by casein kinase II in vivo at three serine residues located at the N and C termini of the protein. Alanine substitution mutations in the casein kinase II target phosphorylation sites dramatically reduce the heterochromatin binding activity of HP1, whereas glutamate substitution mutations, which mimic the charge contributions of phosphorylated serine, have apparently wild-type binding activity. We propose that phosphorylation of HP1 promotes protein-protein interaction between HP1 and target binding proteins in heterochromatin.

Animals↗
PubMed2000

Differences in the meiotic pairing behavior of gonosomal heterochromatin between female and male Microtus agrestis: implications for the mechanism of heterochromatin amplification on the X and Y.

It is generally thought that pairing and recombination between the X and Y chromosome in eutherian mammals is important for the occurrence of normal meiotic division and the production of functional gametes. Microtus agrestis is one of the examples whose giant and heterochromatin-rich sex chromosomes fail to establish a durable association at any stage of the first meiotic division in males. In contrast, in females, synapsis starts in the euchromatic short arm and pairing progresses unidirectionally and continues until both X chromosomes have paired completely, as can be demonstrated by the use of fluorescence in situ hybridization with a sequence confined to the non-centromeric, gonosomal heterochromatin. However, compared with euchromatin, this association is apparently ephemeral and breaks off precociously in the pachytene and metaphase I stages. We demonstrate that a middle repetitive element is localized interspersed in the noncentromeric heterochromatin of both X and Y, except the telomeric region of the Y. No differences could be detected at the molecular level between male and female DNA, indicating that at least the bulk of these elements are organized in the same manner on the X and Y. Our data imply that the loss of synapsis and recombination between the X and Y might have preceded the process of heterochromatin amplification in the course of Microtinae evolution. Since asynapsed elements are particularly susceptible to DNA strand breaks during prophase I, DNA repair of double-strand breaks involving heterochromatic segments of the X and Y could have resulted in translocations of larger segments from the X to the Y or vice versa during the course of chromosome evolution of the gonosomes, explaining the homology at the molecular level between the heterochromatin of the asynaptic X and Y in M. agrestis.

Animals↗
PubMed1979

A comparison of constitutive heterochromatin staining methods in two cases of familial heterochromatin deficiencies.

Using DAPI staining after pretreatment with distamycin A we detected a familial deficiency of chromosome 16 heterochromatin. A distinct positively staining band, however, was seen after C-banding. Thus, by using these different heterochromatin staining methods, heterogeneity of the constitutive heterochromatin in the centromeric region of human chromosome 16 was indicated. The same C-banding procedure was also applied to a previously described familial deficiency of chromosome 9 heterochromatin evidenced using distamycin A/DAPI staining and G 11 staining (Buys et al., 1979). In this case a C-band appeared to be virtually absent on the relevant chromosome. These staining methods may be valuable tools in the study of chromosome polymorphisms.

Azure Stains↗
PubMed1985

Equilocality of heterochromatin distribution and heterochromatin heterogeneity in acridid grasshoppers.

Comparative fluorescence studies on the chromosome of ten species of acridid grasshoppers, with varying amounts and locations of C-band positive heterochromatin, indicate that the only regions to fluoresce differentially are those that C-band. Within a given species there is a marked tendency for groups of chromosomes to accumulate heterochromatin with similar fluorescence behaviour at similar sites. This applies to all three major categories of heterochromatin - centric, interstitial and telomeric. Different sites within the same complement, however, tend to have different fluorescence properties. In particular, centric C-bands within a given species are regularly distinguishable in their behaviour from telomeric C-bands. Different species on the other hand, may show distinct forms of differential fluorescence at equilocal sites. These varying patterns of heterochromatin heterogeneity, both within and between species, indicate that whatever determines the differential response to fluorochromes has tended to operate both on an equilocal basis and in a concerted fashion. This is reinforced by the fact that structural rearrangements that lead to the relocation of centric C-bands, either within or between species, may also be accompanied by a change in fluorescence behaviour.

Animals↗