Interplay of pericentromeric genome organization and chromatin landscape regulates the expression of Drosophila melanogaster heterochromatic genes
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ABSTRACT:
ORGANISM(S): Drosophila melanogaster
PROVIDER: GSE126952 | GEO | 2020/10/08
REPOSITORIES: GEO
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Project description:BackgroundTranscription of genes residing within constitutive heterochromatin is paradoxical to the tenets of epigenetic code. The regulatory mechanisms of Drosophila melanogaster heterochromatic gene transcription remain largely unknown. Emerging evidence suggests that genome organization and transcriptional regulation are inter-linked. However, the pericentromeric genome organization is relatively less studied. Therefore, we sought to characterize the pericentromeric genome organization and understand how this organization along with the pericentromeric factors influences heterochromatic gene expression.ResultsHere, we characterized the pericentromeric genome organization in Drosophila melanogaster using 5C sequencing. Heterochromatic topologically associating domains (Het TADs) correlate with distinct epigenomic domains of active and repressed heterochromatic genes at the pericentromeres. These genes are known to depend on the heterochromatic landscape for their expression. However, HP1a or Su(var)3-9 RNAi has minimal effects on heterochromatic gene expression, despite causing significant changes in the global Het TAD organization. Probing further into this observation, we report the role of two other chromatin proteins enriched at the pericentromeres-dMES-4 and dADD1 in regulating the expression of a subset of heterochromatic genes.ConclusionsDistinct pericentromeric genome organization and chromatin landscapes maintained by the interplay of heterochromatic factors (HP1a, H3K9me3, dMES-4 and dADD1) are sufficient to support heterochromatic gene expression despite the loss of global Het TAD structure. These findings open new avenues for future investigations into the mechanisms of heterochromatic gene expression.
| S-EPMC7541242 | biostudies-literature
Project description:Transcription of genes residing within constitutive heterochromatin is paradoxical to the tenets of epigenetic code. Regulatory mechanisms of Drosophila melanogaster heterochromatic gene transcription remain largely unknown. We investigated the contribution of pericentromeric genome organization and heterochromatic factors in orchestrating heterochromatic gene expression. Using 5C-seq, we characterized the pericentromeric TADs in Drosophila melanogaster. Het TAD borders are enriched in nuclear matrix attachment regions while the intra-TAD interactions are mediated by various insulator binding proteins. Heterochromatic genes of similar expression levels cluster into Het TADs, indicating transcriptional co-regulation. HP1a or Su(var)3-9 RNAi results in perturbation of global pericentromeric TAD organization but the expression of the heterochromatic genes is minimally affected. A subset of active heterochromatic genes has been shown to have combination of HP1a/H3K9me3 with H3K36me3 at their exons. Consequently, knock-down of dMES-4 (H3K36 methyl transferase) downregulates expression of the heterochromatic genes. Furthermore, dADD1, present near the TSS of the active heterochromatic genes, is likely to regulate the heterochromatic gene expression in the presence of HP1a or H3K9me3 marks. Therefore, our findings provide mechanistic insights into the interplay of chromatin interactions and the combination of heterochromatic factors (HP1a, H3K9me3, dMES-4 and dADD1) in regulating heterochromatic gene expression.
2020-10-08 | GSE126951 | GEO
Project description:Transcription of genes residing within constitutive heterochromatin is paradoxical to the tenets of epigenetic code. Regulatory mechanisms of Drosophila melanogaster heterochromatic gene transcription remain largely unknown. We investigated the contribution of pericentromeric genome organization and heterochromatic factors in orchestrating heterochromatic gene expression. Using 5C-seq, we characterized the pericentromeric TADs in Drosophila melanogaster. Het TAD borders are enriched in nuclear matrix attachment regions while the intra-TAD interactions are mediated by various insulator binding proteins. Heterochromatic genes of similar expression levels cluster into Het TADs, indicating transcriptional co-regulation. HP1a or Su(var)3-9 RNAi results in perturbation of global pericentromeric TAD organization but the expression of the heterochromatic genes is minimally affected. A subset of active heterochromatic genes has been shown to have combination of HP1a/H3K9me3 with H3K36me3 at their exons. Consequently, knock-down of dMES-4 (H3K36 methyl transferase) downregulates expression of the heterochromatic genes. Furthermore, dADD1, present near the TSS of the active heterochromatic genes, is likely to regulate the heterochromatic gene expression in the presence of HP1a or H3K9me3 marks. Therefore, our findings provide mechanistic insights into the interplay of chromatin interactions and the combination of heterochromatic factors (HP1a, H3K9me3, dMES-4 and dADD1) in regulating heterochromatic gene expression.
2020-10-08 | GSE126950 | GEO
Project description:Interplay of pericentromeric genome organization and chromatin landscape regulates the expression of Drosophila melanogaster heterochromatic genes
| PRJNA523829 | ENA
Project description:Interplay of pericentromeric genome organization and chromatin landscape regulates the expression of Drosophila melanogaster heterochromatic genes [5C]
| PRJNA523833 | ENA
Project description:Interplay of pericentromeric genome organization and chromatin landscape regulates the expression of Drosophila melanogaster heterochromatic genes [RNA-seq]
| PRJNA523832 | ENA
Project description:Dosage compensation modifies the chromatin of X-linked genes to assure equivalent expression in sexes with unequal X chromosome dosage. In Drosophila dosage compensation is achieved by increasing expression from the male X chromosome. The ribonucleoprotein dosage compensation complex (DCC) binds hundreds of sites along the X chromosome and modifies chromatin to facilitate transcription. Loss of roX RNA, an essential component of the DCC, reduces expression from X-linked genes. Surprisingly, loss of roX RNA also reduces expression from genes situated in proximal heterochromatin and on the small, heterochromatic fourth chromosome. Mutation of some, but not all, of the genes encoding DCC proteins produces a similar effect. Reduction of roX function suppresses position effect variegation (PEV), revealing functional alteration in heterochromatin. The effects of roX mutations on heterochromatic gene expression and PEV are limited to males. A sex-limited role for the roX RNAs in autosomal gene expression was unexpected. We propose that this reflects a difference in the heterochromatin of males and females, which serves to accommodate the heterochromatic Y chromosome present in the male nucleus. roX transcripts may thus participate in two distinct regulatory systems that have evolved in response to highly differentiated sex chromosomes: compensation of X-linked gene dosage and modulation of heterochromatin.
| S-EPMC2691757 | biostudies-literature
Project description:Chromatin is composed of DNA and a variety of modified histones and non-histone proteins, which have an impact on cell differentiation, gene regulation and other key cellular processes. Here we present a genome-wide chromatin landscape for Drosophila melanogaster based on eighteen histone modifications, summarized by nine prevalent combinatorial patterns. Integrative analysis with other data (non-histone chromatin proteins, DNase I hypersensitivity, GRO-Seq reads produced by engaged polymerase, short/long RNA products) reveals discrete characteristics of chromosomes, genes, regulatory elements and other functional domains. We find that active genes display distinct chromatin signatures that are correlated with disparate gene lengths, exon patterns, regulatory functions and genomic contexts. We also demonstrate a diversity of signatures among Polycomb targets that include a subset with paused polymerase. This systematic profiling and integrative analysis of chromatin signatures provides insights into how genomic elements are regulated, and will serve as a resource for future experimental investigations of genome structure and function.
| S-EPMC3109908 | biostudies-literature
Project description:In the nucleus of eukaryotic cells, genomic DNA associates with numerous protein complexes and RNAs, forming the chromatin landscape. Through a genome-wide study of chromatin-associated proteins in Drosophila cells, five major chromatin types were identified as a refinement of the traditional binary division into hetero- and euchromatin. These five types were given color names in reference to the Greek word chroma. They are defined by distinct but overlapping combinations of proteins and differ in biological and biochemical properties, including transcriptional activity, replication timing, and histone modifications. In this work, we assess the evolutionary relationships of chromatin-associated proteins and present an integrated view of the evolution and conservation of the fruit fly Drosophila melanogaster chromatin landscape. We combine homology prediction across a wide range of species with gene age inference methods to determine the origin of each chromatin-associated protein. This provides insight into the evolution of the different chromatin types. Our results indicate that for the euchromatic types, YELLOW and RED, young associated proteins are more specialized than old ones; and for genes found in either chromatin type, intron/exon structure is lineage-specific. Next, we provide evidence that a subset of GREEN-associated proteins is involved in a centromere drive in D. melanogaster. Our results on BLUE chromatin support the hypothesis that the emergence of Polycomb Group proteins is linked to eukaryotic multicellularity. In light of these results, we discuss how the regulatory complexification of chromatin links to the origins of eukaryotic multicellularity.
| S-EPMC6411481 | biostudies-literature
Project description:Constitutive heterochromatin is enriched in repetitive sequences and histone H3-methylated-at-lysine 9. Both components contribute to heterochromatin's ability to silence euchromatic genes. However, heterochromatin also harbors hundreds of expressed genes in organisms such as Drosophila. Recent studies have provided a detailed picture of sequence organization of D. melanogaster heterochromatin, but how histone modifications are associated with heterochromatic sequences at high resolution has not been described. Here, distributions of modified histones in the vicinity of heterochromatic genes of normal embryos and embryos homozygous for a chromosome rearrangement were characterized using chromatin immunoprecipitation and genome tiling arrays. We found that H3-di-methylated-at-lysine 9 (H3K9me2) was depleted at the 5' ends but enriched throughout transcribed regions of heterochromatic genes. The profile was distinct from that of euchromatic genes and suggests that heterochromatic genes are integrated into, rather than insulated from, the H3K9me2-enriched domain. Moreover, the profile was only subtly affected by a Su(var)3-9 null mutation, implicating a histone methyltransferase other than SU(VAR)3-9 as responsible for most H3K9me2 associated with heterochromatic genes in embryos. On a chromosomal scale, we observed a sharp transition to the H3K9me2 domain, which coincided with increased retrotransposon density in the euchromatin-heterochromatin (eu-het) transition zones on the long chromosome arms. Thus, a certain density of retrotransposons, rather than specific boundary elements, may demarcate Drosophila pericentric heterochromatin. We also demonstrate that a chromosome rearrangement that created a new eu-het junction altered H3K9me2 distribution and induced new euchromatic sites of enrichment as far as several megabases away from the breakpoint. Taken together, the findings argue against simple classification of H3K9me as the definitive signature of silenced genes, and clarify roles of histone modifications and repetitive DNAs in heterochromatin. The results are also relevant for understanding the effects of chromosome aberrations and the megabase scale over which epigenetic position effects can operate in multicellular organisms.
| S-EPMC2211541 | biostudies-literature