The Heterochromatin Protein 1 Prevents Telomere Fusions in Drosophila

Fanti, Laura; Giovinazzo, Giovanna; Berloco, Maria; Pimpinelli, Sergio

doi:10.1016/s1097-2765(00)80152-5

Cited by 267 publications

(305 citation statements)

References 54 publications

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“…Several observations, however, indicate that the contribution of WOC/ROW/HP1c is not related to that of HP1a. On one hand, su(var)2-5 mutants show much stronger effects than either woc or row mutants (Fanti et al 1998;Raffa et al 2005). Furthermore, both telomere length and expression of the telomeric retrotransposons Het-A and TART are increased in su-(var)2-5 mutants, but they are not affected in woc-null mutants (Perrini et al 2004;Raffa et al 2005).…”

Section: Hp1c and Telomere Functionmentioning

confidence: 97%

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Drosophila HP1c isoform interacts with the zinc-finger proteins WOC and Relative-of-WOC to regulate gene expression

Font-Burgada¹,

Rossell²,

Auer³

et al. 2008

Genes Dev.

129

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Heterochromatin protein 1 (HP1) proteins are conserved in eukaryotes, with most species containing several isoforms. Based on the properties of Drosophila HP1a, it was proposed that HP1s bind H3K9me2,3 and recruit factors involved in heterochromatin assembly and silencing. Yet, it is unclear whether this general picture applies to all HP1 isoforms and functional contexts. Here, we report that Drosophila HP1c regulates gene expression, as (1) it localizes to active chromatin domains, where it extensively colocalizes with the poised form of RNApolymerase II (RNApol II), Pol IIo ser5 , and H3K4me3, suggesting a contribution to transcriptional regulation; (2) its targeting to a reporter gene does not induce silencing but, on the contrary, increases its expression, and (3) it interacts with the zinc-finger proteins WOC (without children) and Relative-of-WOC (ROW), which are putative transcription factors. Here, we also show that, although HP1c efficiently binds H3K9me2,3 in vitro, its binding to chromatin strictly depends on both WOC and ROW. Moreover, expression profiling indicates that HP1c, WOC, and ROW regulate a common gene expression program that, in part, is executed in the context of the nervous system. From this study, which unveils the essential contribution of DNA-binding proteins to HP1c functionality and recruitment, HP1 proteins emerge as an increasingly diverse family of chromatin regulators.[Keywords: HP1; WOC; ROW/CG8092; chromatin; Drosophila] Supplemental material is available at http://www.genesdev.org.

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Section: Hp1c and Telomere Functionmentioning

confidence: 97%

“…HP1a is also known to regulate telomere function (Fanti et al 1998). Several observations, however, indicate that the contribution of WOC/ROW/HP1c is not related to that of HP1a.…”

Section: Hp1c and Telomere Functionmentioning

confidence: 99%

Drosophila HP1c isoform interacts with the zinc-finger proteins WOC and Relative-of-WOC to regulate gene expression

Font-Burgada¹,

Rossell²,

Auer³

et al. 2008

Genes Dev.

129

View full text Add to dashboard Cite

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“…Nevertheless, the phenotypes of HP1 mutants indicate that if such interactions do occur, they are not critical for Nipped-B and cohesin function. It has been reported that polytene chromosomes appear relatively normal in HP1 [Su(var)2-5] mutants and cohesion defects do not occur in any of the several tissues examined (Fanti et al 1998). Polytene chromosomes that lack cohesin, on the other hand, show a significant change in morphology (Dorsett et al 2005).…”

Section: Nipped-b Cohesin and Pds5 Colocalize On Salivary Polytene mentioning

confidence: 97%

Functional links between Drosophila Nipped-B and cohesin in somatic and meiotic cells

et al. 2007

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Drosophila Nipped-B is an essential protein that has multiple functions. It facilitates expression of homeobox genes and is also required for sister chromatid cohesion. Nipped-B is conserved from yeast to man, and its orthologs also play roles in deoxyribonucleic acid repair and meiosis. Mutation of the human ortholog, Nipped-B-Like (NIPBL), causes Cornelia de Lange syndrome (CdLS), associated with multiple developmental defects. The Nipped-B protein family is required for the cohesin complex that mediates sister chromatid cohesion to bind to chromosomes. A key question, therefore, is whether the Nipped-B family regulates gene expression, meiosis, and development by controlling cohesin. To gain insights into Nipped-B's functions, we compared the effects of several Nipped-B mutations on gene expression, sister chromatid cohesion, and meiosis. We also examined association of Nipped-B and cohesin with somatic and meiotic chromosomes by immunostaining. Missense Nipped-B alleles affecting the same HEAT repeat motifs as CdLS-causing NIPBL mutations have intermediate effects on both gene expression and mitotic chromatid cohesion, linking these two functions and the role of NIPBL in human development. Nipped-B colocalizes extensively with cohesin on chromosomes in both somatic and meiotic cells and is present in soluble complexes

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“…Telomeres are heterochromatic regions. Yeast and flies with defects in activities that modify the state of chromatin also have abnormal telomere function [4][5][6] , but the putative role of chromatin-modifying activities in regulating telomeres in mammals is unknown. Here we report on telomere length and function in mice null with respect to both the histone methyltransferases (HMTases) Suv39h1 and Suv39h2 (called SUV39DN mice).…”

mentioning

confidence: 99%

“…Heterochromatic regions are enriched in methylated H3-Lys9, which creates a binding site for the chromobox proteins 9 , mediators of heterochromatin formation and epigenetic gene regulation. In D. melanogaster, HP1 is also required for telomere capping 4,5 . To investigate the impact of H3-Lys9 methylation on telomere length regulation and telomere function, we studied embryonic stem (ES) cells and mouse embryonic fibroblasts (MEFs) from SUV39DN mice 7 , which have less methylation of H3-Lys9 at the pericentric heterochromatin compared to wildtype mice 7 .…”

mentioning

confidence: 99%

Epigenetic regulation of telomere length in mammalian cells by the Suv39h1 and Suv39h2 histone methyltransferases

et al. 2003

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Telomeres are capping structures at the ends of eukaryotic chromosomes composed of TTAGGG repeats bound to an array of specialized proteins 1-3 . Telomeres are heterochromatic regions. Yeast and flies with defects in activities that modify the state of chromatin also have abnormal telomere function 4-6 , but the putative role of chromatin-modifying activities in regulating telomeres in mammals is unknown. Here we report on telomere length and function in mice null with respect to both the histone methyltransferases (HMTases) Suv39h1 and Suv39h2 (called SUV39DN mice). Suv39h1 and Suv39h2 govern methylation of histone H3 Lys9 (H3-Lys9) in heterochromatic regions 7 . We show that primary cells derived from SUV39DN mice have abnormally long telomeres relative to wild-type controls. Using chromatin immunoprecipitation (ChIP) analysis, we found that telomeres were enriched in diand trimethylated H3-Lys9 but that telomeres of SUV39DN cells had less dimethylated and trimethylated H3-Lys9 but more monomethylated H3-Lys9. Concomitant with the decrease in H3-Lys9 methylation, telomeres in SUV39DN cells had reduced binding of the chromobox proteins Cbx1, Cbx3 and Cbx5, homologs of Drosophila melanogaster heterochromatin protein 1 (HP1). These findings indicate substantial changes in the state of telomeric heterochromatin in SUV39DN cells, which are associated with abnormal telomere elongation. Taken together, the results indicate epigenetic regulation of telomere length in mammals by Suv39h1 and Suv39h2.The N-terminal tails of histones are subjected to post-translational modifications, including acetylation, methylation and phosphorylation, generating an extensive repertoire of chromatin structures 8,9 . Binding of factors that specifically recognize these modified histones mediate cellular responses 8,9 . Heterochromatic regions are enriched in methylated H3-Lys9, which creates a binding site for the chromobox proteins 9 , mediators of heterochromatin formation and epigenetic gene regulation. In D. melanogaster, HP1 is also required for telomere capping 4,5 . To investigate the impact of H3-Lys9 methylation on telomere length regulation and telomere function, we studied embryonic stem (ES) cells and mouse embryonic fibroblasts (MEFs) from SUV39DN mice 7 , which have less methylation of H3-Lys9 at the pericentric heterochromatin compared to wildtype mice 7 . First, we used terminal restriction fragment (TRF) analysis to estimate telomere length in these cells. Two independent SUV39DN ES cell cultures showed abnormally long telomeres, which were not present in wild-type ES cells (Fig. 1a). This finding was confirmed using MEFs (passage 1-2) derived from SUV39DN and wild-type littermate embryos (Fig. 1a). TRF analysis of increasing passages of the SUV39DN MEFs (D43) showed that the long telomeres in these MEFs were stable (Fig. 1b).Next, we carried out quantitative fluorescence in situ hybridization (Q-FISH) using a telomere-specific peptide nucleic acid probe. We determined the average telomere length for each ES-cell and ME...

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The Heterochromatin Protein 1 Prevents Telomere Fusions in Drosophila

Cited by 267 publications

References 54 publications

Drosophila HP1c isoform interacts with the zinc-finger proteins WOC and Relative-of-WOC to regulate gene expression

Drosophila HP1c isoform interacts with the zinc-finger proteins WOC and Relative-of-WOC to regulate gene expression

Functional links between Drosophila Nipped-B and cohesin in somatic and meiotic cells

Epigenetic regulation of telomere length in mammalian cells by the Suv39h1 and Suv39h2 histone methyltransferases

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