The establishment of HP1-independent heterochromatin reveals an essential role for HP1 proteins in maintaining epigenetic memory
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ABSTRACT:
PROVIDER: PRJNA967013 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR24423061_1.fastq.gz | Fastqsanger.gz | |||
| SRR24423061_2.fastq.gz | Fastqsanger.gz | |||
| SRR24423062_1.fastq.gz | Fastqsanger.gz | |||
| SRR24423062_2.fastq.gz | Fastqsanger.gz | |||
| SRR24423063_1.fastq.gz | Fastqsanger.gz |
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Project description:H3K9 methylation (H3K9me) marks transcriptionally silent genomic regions called heterochromatin. A conserved class of HP1 proteins are critically required to establish and maintain heterochromatin. HP1 proteins bind to H3K9me, recruit factors that promote heterochromatin formation, and oligomerize to form phase-separated condensates. We do not understand how HP1 protein binding to heterochromatin establishes and maintains transcriptional silencing. Here, we demonstrate that the S.pombe HP1 homolog, Swi6, can be completely bypassed to establish silencing at ectopic and endogenous loci when an H3K4 methyltransferase, Set1 and an H3K14 acetyltransferase, Mst2 are deleted. Deleting Set1 and Mst2 enhances Clr4 enzymatic activity, leading to higher H3K9me levels and increased spreading. In contrast, Swi6 and its capacity to oligomerize were indispensable during epigenetic maintenance. Our results demonstrate the role of HP1 proteins in regulating histone modification crosstalk during establishment and identifies a genetically separable function in maintaining epigenetic memory.
2023-05-24 | GSE233333 | GEO
Project description:H3K9 methylation (H3K9me) marks transcriptionally silent genomic regions called heterochromatin. A conserved class of HP1 proteins are critically required to establish and maintain heterochromatin. HP1 proteins bind to H3K9me, recruit factors that promote heterochromatin formation, and oligomerize to form phase-separated condensates. We do not understand how HP1 protein binding to heterochromatin establishes and maintains transcriptional silencing. Here, we demonstrate that the S.pombe HP1 homolog, Swi6, can be completely bypassed to establish silencing at ectopic and endogenous loci when an H3K4 methyltransferase, Set1 and an H3K14 acetyltransferase, Mst2 are deleted. Deleting Set1 and Mst2 enhances Clr4 enzymatic activity, leading to higher H3K9me levels and increased spreading. In contrast, Swi6 and its capacity to oligomerize were indispensable during epigenetic maintenance. Our results demonstrate the role of HP1 proteins in regulating histone modification crosstalk during establishment and identifies a genetically separable function in maintaining epigenetic memory.
2023-05-10 | GSE231618 | GEO
Project description:The establishment of HP1-independent heterochromatin reveals an essential role for HP1 proteins in maintaining epigenetic memory.
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Project description:H3K9 methylation (H3K9me) marks transcriptionally silent genomic regions called heterochromatin. A conserved class of HP1 proteins are critically required to establish and maintain heterochromatin. HP1 proteins bind to H3K9me, recruit factors that promote heterochromatin formation, and oligomerize to form phase-separated condensates. We do not understand how HP1 protein binding to heterochromatin establishes and maintains transcriptional silencing. Here, we demonstrate that the S.pombe HP1 homolog, Swi6, can be completely bypassed to establish silencing at ectopic and endogenous loci when an H3K4 methyltransferase, Set1 and an H3K14 acetyltransferase, Mst2 are deleted. Deleting Set1 and Mst2 enhances Clr4 enzymatic activity, leading to higher H3K9me levels and increased spreading. In contrast, Swi6 and its capacity to oligomerize were indispensable during epigenetic maintenance. Our results demonstrate the role of HP1 proteins in regulating histone modification crosstalk during establishment and identifies a genetically separable function in maintaining epigenetic memory.
2023-09-26 | GSE244017 | GEO
Project description:Uncoupling the distinct functions of HP1 proteins during heterochromatin establishment and maintenance
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Project description:HP1 proteins bind dynamically to H3K9 methylation and are essential for establishing and maintaining transcriptionally silent epigenetic states, known as heterochromatin. HP1 proteins can dimerize, forming a binding interface that interacts with and recruits diverse chromatin-associated factors. HP1 proteins rapidly evolve through sequence changes and gene duplications, but the extent of variation required to achieve functional specialization is unknown. To investigate how changes in amino acid sequence impact epigenetic inheritance, we performed a targeted mutagenesis screen of the dimerization and protein interaction domain of the S.pombe HP1 homolog Swi6. We discovered that substitutions mapping to an auxiliary motif in Swi6 outside the dimerization interface can lead to complete functional divergence. Specifically, we identified point mutations at a single amino acid residue that resulted in either persistent gain or loss of function in epigenetic inheritance without affecting heterochromatin establishment. These substitutions increase Swi6 chromatin occupancy in vivo and alter Swi6-protein interactions that selectively affect H3K9me inheritance. Based on our findings, we propose that relatively minor changes in Swi6 amino acid composition can lead to profound changes in epigenetic inheritance, underscoring the remarkable plasticity associated with HP1 proteins and their ability to evolve new functions.
2024-08-10 | PXD047651 | Pride
Project description:The replication of a genomic region during S-phase can be highly dynamic between cell types that differ in transcriptome and epigenome. Replication timing has been positively correlated with several histone modifications that occur at active genes, while repressive histone modifications mark late replicating regions. This raises the question if chromatin modulates the initiating events of replication. To gain insights into this question we have studied the function of heterochromatin protein 1 (HP1), a reader of to the repressive histone lysine 9 methylation of H3, in genome-wide organization of replication. Cells with reduced levels of HP1 show an advanced replication timing of centromeric repeats in agreement with the model that repressive chromatin mediates the very late replication of large clusters of constitutive heterochromatin. Surprisingly however regions with high levels of interspersed repeats on the chromosomal arms in particular on chromosome 4 and in pericentromeric regions of chromosome 2 behave differently. Here loss of HP1 results in delayed replication timing. The fact that these regions are bound by HP1 suggests a direct effect. Thus while HP1 mediates very late replication of centromeric DNA it is also required for early replication of autosomal regions with high levels of repeats. This observation of opposing functions of HP1 suggests a model where repeat inactivation on autosomes is required for proper activation of origins of replication that fire early, while HP1 mediated repression at constitutive heterochromatin is required to ensure replication of centromeric repeats at the end of S phase. Keywords: RNAi, chip-chip, replication timing
2010-03-16 | GSE18092 | GEO
Project description:Heterochromatin is important for the maintenance of genome stability and regulation of gene expression, yet our knowledge of heterochromatin structure and function is incomplete. We identified four novel Drosophila heterochromatin proteins. Three of these proteins (HP3, HP4, and HP5) interact directly with HP1, while HP6 in turn binds to each of these three proteins. Immunofluorescence microscopy and genome-wide mapping of in vivo binding sites shows that all four proteins are components of heterochromatin. Depletion of HP1 causes redistribution of all four proteins, indicating that HP1 is essential for their heterochromatic targeting. Finally, mutants of HP4 and HP5 are dominant suppressors of position effect variegation, demonstrating their importance in heterochromatic gene silencing. These results indicate that HP1 acts as a docking platform for several mediator proteins that contribute to heterochromatin function. Keywords: DamID knock-down
2007-02-02 | GSE6411 | GEO
Project description:Both RNAi-dependent and -independent mechanisms have been implicated in the establishment of heterochromatin domains, which may be stabilized by feedback loops involving chromatin proteins and modifications of histones and DNA. Neurospora crassa sports features of heterochromatin found in higher eukaryotes, namely cytosine methylation (5mC), methylation of histone H3 lysine9 (H3K9me) and HETEROCHROMATIN PROTEIN-1 (HP1), and provides a model to investigate heterochromatin establishment and maintenance. We mapped the distribution of HP1, 5mC, H3K9me3 and H3K4me2 at 100bp-resolution and explored their interplay. HP1, H3K9me3 and DNA methylation were extensively colocalized and defined 44 heterochromatic domains on linkage group VII, all relics of repeat-induced point mutation (RIP). Interestingly, the centromere was found in a striking ~350kb heterochromatic domain with no detectable H3K4me2. 5mC was not found in genes, in contrast to the situation in plants and animals. H3K9me3 is required for HP1 localization and DNA methylation. Here, we show that localization of H3K9me3 is independent of 5mC or HP1 at virtually all heterochromatin regions. In addition, we observed complete restoration of DNA methylation patterns after depletion and reintroduction of the H3K9 methylation machinery, indicating that the signals for de novo heterochromatin formation lie upstream of H3K9 methylation. These data show that A:T rich RIPâd DNA efficently directs methylation of H3K9, which in turn, directs methylation of associated cytosines. Immunoprecipitation experiments using antibodies to 5mC, H3K9me3, epitope-tagged HP1, and H3K4me2 were performed. The immunoprecipitate fraction was labeled with Cy5 and the total input was labeled with Cy3. Samples were hybridized to a N. crassa LGVII tiling path microarray.
2010-05-15 | E-GEOD-12690 | biostudies-arrayexpress
Project description:The family of Heterochromatin Protein 1 (HP1) consists of highly conserved proteins, which have important functions in the nucleus of eukaryotic cells. In mammals there are three HP1 paralogs: HP1(alpha), Hp1(beta), and Hp1(gamma)They are encoded by the Cbx5, Cbx1, and Cbx3 genes, respectively. Hp1 and Hp1 stably interact with Chd4 and Adnp to form the ChAHP complex. In this project, Chd4, Adnp, and the three Cbx genes were endogenously tagged with a FLAG-Avi tag in mouse embryonic stem cells. The tagged proteins were subjected to tandem-affinity purification and analysis by mass spectrometry.
2018-05-22 | PXD006226 | Pride