Heterochromatin protein 1: a pervasive controlling influence

Hiragami, K.; Festenstein, Richard

doi:10.1007/s00018-005-5287-9

Cited by 118 publications

(126 citation statements)

References 154 publications

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“…These results indicate that chromosomal association of HP1c is largely determined by the recognition of specific DNA sequences, which is in contrast to the situation observed in the case of Drosophila HP1a, or mammalian HP1␣, where chromosomal association was found to depend on The observed correlations are compared with the range expected if no genes were coregulated and if all were coregulated. the recognition of a specific pattern of histone modifications; namely, H3K9 methylation (Hiragami and Festenstein 2005;Hediger and Gasser 2006). Several HP1 proteins, including HP1a and HP1␣, were reported to interact with a number of transcription factors, replication proteins, and chromatin assembly complexes (Hiragami and Festenstein 2005;Hediger and Gasser 2006;Lomberk et al 2006).…”

Section: Binding Of Hp1c To Chromatin Relies On the Zinc-finger Protementioning

confidence: 99%

“…the recognition of a specific pattern of histone modifications; namely, H3K9 methylation (Hiragami and Festenstein 2005;Hediger and Gasser 2006). Several HP1 proteins, including HP1a and HP1␣, were reported to interact with a number of transcription factors, replication proteins, and chromatin assembly complexes (Hiragami and Festenstein 2005;Hediger and Gasser 2006;Lomberk et al 2006). Yet, it is unclear whether these interactions mediate recruitment of HP1 to specific sites, and/or in response to particular processes, or they actually take place after recruitment to regulate their functions.…”

Section: Binding Of Hp1c To Chromatin Relies On the Zinc-finger Protementioning

confidence: 99%

“…Most frequently, regulation by chromatin involves the establishment of specific patterns of post-translational histone modifications, which result in recruitment of regulatory nonhistone proteins (Ruthenburg et al 2007). Heterochromatin protein 1 (HP1) constitutes one of the best-studied examples (Hiragami and Festenstein 2005;Hediger and Gasser 2006;Lomberk et al 2006), where a regulatory nonhistone protein is recruited to chromatin through the recognition of a specific histone modification, dior trimethylation of Lys 9 on the histone H3 tail (H3K9me2,3). This interaction, which involves the Nterminal chromodomain of HP1, is known to play a fundamental role in the formation and maintenance of heterochromatic domains.…”

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confidence: 99%

“…Except in budding yeast, HP1 is widely conserved in eukaryotes, with most species containing several isoforms (Hiragami and Festenstein 2005;Lomberk et al 2006). HP1 proteins are characterized by a common structural organization consisting of two conserved domains, the N-terminal chromodomain and the C-terminal chromo-shadow domain, which are spaced by a variable nonconserved hinge domain.…”

mentioning

confidence: 99%

“…Most of our knowledge about the mechanisms of action of HP1 proteins derives from studies addressing the functional properties of Drosophila HP1a or mammalian HP1␣. From these studies, a general picture emerges by which, through the chromodomain, HP1 proteins bind chromatin regions enriched in H3K9me2,3 while, through the chromo-shadow domain, recruiting different factors resulting in various functional outcomes; namely, heterochromatin assembly and gene silencing (Hiragami and Festenstein 2005;Hediger and Gasser 2006;Lomberk et al 2006). It is uncertain whether this general picture applies to all HP1 proteins and possible scenarios.…”

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confidence: 99%

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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: Binding Of Hp1c To Chromatin Relies On the Zinc-finger Protementioning

confidence: 99%

Section: Binding Of Hp1c To Chromatin Relies On the Zinc-finger Protementioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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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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The HP1a Disordered C Terminus and Chromo Shadow Domain Cooperate to Select Target Peptide Partners

et al. 2011

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Drosophila melanogaster Heterochromatin Protein 1a (HP1a) is essential for compacted heterochromatin structure and associated gene silencing. Its chromo shadow domain (CSD) is well-known for binding to peptides that contain a PXVXL motif. Heterochromatin protein 2 (HP2) is a nonhistone chromosomal protein that associates with HP1a in the pericentric heterochromatin, telomeres and the fourth chromosome. Using NMR spectroscopy, fluorescence polarization and site-directed mutagenesis, we identified an LCVKI motif in HP2 that binds to the HP1a CSD. The binding affinity of the HP2 fragment is approximately two orders of magnitude higher than that of peptides from PIWI (with a PRVKV motif), AF10 (with a PLVVL motif), or CG15356 (with LYPLL and LSIVA motifs). To delineate differential interactions of the HP1a CSD, we characterized its structure, backbone dynamics and dimerization constant. We find that the dimerization constant is bracketed by the affinities of HP2 and PIWI, which dock to the same HP1a homodimer surface. This suggests that HP2, but not PIWI, interaction can drive homodimerization of HP1a. Interestingly, the integrity of the disordered C-terminal extension (CTE) of HP1a is essential for discriminatory binding, whereas swapping the PXVXL motifs does not confer specificity. Serine phosphorylation at the peptide binding surface of the CSD is thought to regulate heterochromatin assembly. Glutamic acid substitution at these sites destabilizes HP1a dimers, but improves the interaction with both binding partners. Our studies underscore the importance of CSD dimerization and cooperation with the CTE in forming distinct complexes of HP1a.

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Analysis of HP1α regulation in human breast cancer cells

Thomsen

Christensen

Rosborg

et al. 2011

Molecular Carcinogenesis

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The three mammalian HP1 proteins, HP1α/CBX5, HP1β/CBX1, and HPγ/CBX3, are involved in chromatin packing and gene regulation. The HP1α protein is down-regulated in invasive compared to non-invasive breast cancer cells and HP1α is a suppressor of cell migration and invasion. In this report, we examined the background for HP1α protein down-regulation in invasive breast cancer cells. We identified a strict correlation between HP1α down-regulation at the protein level and the mRNA level. The HP1α mRNA down-regulation in invasive cancer cells was not caused by mRNA destabilization. Chromatin immunoprecipitation analysis of the HP1α gene showed a decrease in the histone mark for transcriptional activity H3-K36 tri-methylation and RNA polymerase II in invasive breast cancer cells which correlated with a decreased abundance of basal transcription factors at the HP1α promoter. E2F transcription factors regulate HP1α transcription and we identified that E2F5 depletion increased HP1α expression in invasive breast cancer cells. Finally, we have characterized two HP1α mRNA isoforms and both HP1α mRNA isoforms were down-regulated to a similar extend at the transcriptional level in invasive breast cancer cells. Collectively the presented results show that HP1α down-regulation in invasive breast cancer cells is primary a transcriptional effect and demonstrates a novel set of mechanisms involved in HP1α transcriptional regulation. The finding that HP1α is down-regulated primarily at the transcriptional level provides a new insight for the further elucidation of the detailed molecular mechanisms causing the HP1α down-regulation in invasive breast cancer cells.

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Heterochromatin protein 1: a pervasive controlling influence

Cited by 118 publications

References 154 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

The HP1a Disordered C Terminus and Chromo Shadow Domain Cooperate to Select Target Peptide Partners

Analysis of HP1α regulation in human breast cancer cells

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