Chromatin architecture reorganisation during neuronal cell differentiation in Drosophila genome
Ontology highlight
ABSTRACT:
ORGANISM(S): Drosophila melanogaster
PROVIDER: GSE122603 | GEO | 2019/01/18
REPOSITORIES: GEO
Similar Datasets
Project description:Chromosomes of metazoan organisms are partitioned in the interphase nucleus into discrete topologically associating domains (TADs). Borders between TADs are preferentially formed in regions containing high density of active genes and clusters of architectural protein binding sites. Transcription of most genes is turned off during the heat shock response in Drosophila. Here we show that temperature stress induces relocalization of architectural proteins from TAD borders to inside TADs, and this is accompanied by a dramatic rearrangement in the 3D organization of the nucleus. TAD border strength declines, allowing for an increase in long-distance inter-TAD interactions. Similar but quantitatively weaker effects are observed upon inhibition of transcription or depletion of individual architectural proteins. New heat shock-induced inter-TAD interactions result in increased contacts among enhancers and promoters of silenced genes, which recruit Pc and form Pc bodies at the nucleolus. These results suggest that the TAD organization of metazoan genomes is plastic and can be quickly reconfigured to allow new interactions between distant sequences. Analysis of the distribution of architectural proteins, chromatin proteins and histone modifications in Drosophila Kc167 cells. Cells were grown at 25 C (NT) or heat shocked for 20 min at 36.5 C (HS). Both control and reference samples are included. For some of the samples, replicates are also included.
2015-02-24 | E-GEOD-62904 | biostudies-arrayexpress
Project description:Chromosomes of metazoan organisms are partitioned in the interphase nucleus into discrete topologically associating domains (TADs). Borders between TADs are preferentially formed in regions containing high density of active genes and clusters of architectural protein binding sites. Transcription of most genes is turned off during the heat shock response in Drosophila. Here we show that temperature stress induces relocalization of architectural proteins from TAD borders to inside TADs, and this is accompanied by a dramatic rearrangement in the 3D organization of the nucleus. TAD border strength declines, allowing for an increase in long-distance inter-TAD interactions. Similar but quantitatively weaker effects are observed upon inhibition of transcription or depletion of individual architectural proteins. New heat shock-induced inter-TAD interactions result in increased contacts among enhancers and promoters of silenced genes, which recruit Pc and form Pc bodies at the nucleolus. These results suggest that the TAD organization of metazoan genomes is plastic and can be quickly reconfigured to allow new interactions between distant sequences. Analysis of 3D chromatin organization using Hi-C in Drosophila Kc167 cells. Cells were grown at 25 C and heat shocked for 20 min at 36.5 C. Cells were also treated with flavopiridol or triptolide to inhibit transcription elongation or initiation, respectively. Cells were depeleted of Cap-H2 or Rad21 using RNAi. Finally, cells depleted of RAd21 were subjected to heat shock at 36.5 C for 20 min.
2015-02-24 | E-GEOD-63515 | biostudies-arrayexpress
Project description:Maintenance of gene expression programs requires cell-type specific barcoding of genomes through euchromatin interspaced with facultative heterochromatin domains where PRC1/2 hinder chromatin accessibility thereby repressing genes inside such domains. At heterochromatin-euchromatin borders, regulation of heterochromatin spreading may depend on transcriptional activity, histone modifiers, and chromatin barrier insulators or the borders of topological associated domain (TADs). Here we show that depletion of H3K36 di- or tri-methyl histone methyl transferases dMes-4/NSD or Hypb/dSet2 induces H3K27me3 spreading at H3K27me3 borders, accounting for the repression of hundreds of genes upon depletion of these enzymes. dMes-4/NSD influences genes within active chromatin hubs and flanked by H3K27me3 borders demarcated by a TAD border, unlike dHypb/dSet2 that protects genes near H3K27me3 borders in absence of a TAD border. Insulator mutants that disrupt 3D chromatin hubs recapitulate only the H3K27me3 spreading observed upon depletion of dMes-4/NSD, and not of Hypb/dSet2. Hi-C data demonstrate how dMes-4/NSD directly block the propagation of the long-range interactions marking the inactive TADs, onto neighbor active regions, unlike Hypb/dSet2. Our data thus show a division of labor between dMes-4/NSD and Hypb/dSet2 to protect genes against H3K27me3 silencing, highlighting a direct influence of H3K36me marks on the demarcation of H3K27me3 domains within repressive TADs.
2023-07-01 | GSE146993 | GEO
Project description:Maintenance of gene expression programs requires cell-type specific barcoding of genomes through euchromatin interspaced with facultative heterochromatin domains where PRC1/2 hinder chromatin accessibility thereby repressing genes inside such domains. At heterochromatin-euchromatin borders, regulation of heterochromatin spreading may depend on transcriptional activity, histone modifiers, and chromatin barrier insulators or the borders of topological associated domain (TADs). Here we show that depletion of H3K36 di- or tri-methyl histone methyl transferases dMes-4/NSD or Hypb/dSet2 induces H3K27me3 spreading at H3K27me3 borders, accounting for the repression of hundreds of genes upon depletion of these enzymes. dMes-4/NSD influences genes within active chromatin hubs and flanked by H3K27me3 borders demarcated by a TAD border, unlike dHypb/dSet2 that protects genes near H3K27me3 borders in absence of a TAD border. Insulator mutants that disrupt 3D chromatin hubs recapitulate only the H3K27me3 spreading observed upon depletion of dMes-4/NSD, and not of Hypb/dSet2. Hi-C data demonstrate how dMes-4/NSD directly block the propagation of the long-range interactions marking the inactive TADs, onto neighbor active regions, unlike Hypb/dSet2. Our data thus show a division of labor between dMes-4/NSD and Hypb/dSet2 to protect genes against H3K27me3 silencing, highlighting a direct influence of H3K36me marks on the demarcation of H3K27me3 domains within repressive TADs.
2023-07-01 | GSE209956 | GEO
Project description:Maintenance of gene expression programs requires cell-type specific barcoding of genomes through euchromatin interspaced with facultative heterochromatin domains where PRC1/2 hinder chromatin accessibility thereby repressing genes inside such domains. At heterochromatin-euchromatin borders, regulation of heterochromatin spreading may depend on transcriptional activity, histone modifiers, and chromatin barrier insulators or the borders of topological associated domain (TADs). Here we show that depletion of H3K36 di- or tri-methyl histone methyl transferases dMes-4/NSD or Hypb/dSet2 induces H3K27me3 spreading at H3K27me3 borders, accounting for the repression of hundreds of genes upon depletion of these enzymes. dMes-4/NSD influences genes within active chromatin hubs and flanked by H3K27me3 borders demarcated by a TAD border, unlike dHypb/dSet2 that protects genes near H3K27me3 borders in absence of a TAD border. Insulator mutants that disrupt 3D chromatin hubs recapitulate only the H3K27me3 spreading observed upon depletion of dMes-4/NSD, and not of Hypb/dSet2. Hi-C data demonstrate how dMes-4/NSD directly block the propagation of the long-range interactions marking the inactive TADs, onto neighbor active regions, unlike Hypb/dSet2. Our data thus show a division of labor between dMes-4/NSD and Hypb/dSet2 to protect genes against H3K27me3 silencing, highlighting a direct influence of H3K36me marks on the demarcation of H3K27me3 domains within repressive TADs.
2023-07-01 | GSE146992 | GEO
Project description:Recent advances enabled by Hi-C technique have unraveled principles of chromosomal folding, which were since linked to many genomic processes. In particular, Hi-C revealed that chromosomes of animals are organized into Topologically Associating Domains (TADs), evolutionary conserved compact chromatin domains that influence gene expression. However, mechanisms that underlie partitioning of the genome into TADs remain poorly understood. To explore principals of TAD folding in Drosophila melanogaster, we performed Hi-C and PolyA+ RNA-seq in four cell lines of various origins (S2, Kc167, DmBG3-c2, and OSC). Contrary to previous studies, we find that regions between TADs (i.e. the inter-TADs and TAD boundaries) in Drosophila are only weakly enriched with the insulator protein dCTCF, while another insulator protein Su(Hw) is preferentially present within TADs. However, Drosophila inter-TADs harbor active chromatin and constitutively transcribed (housekeeping) genes. Accordingly, we find that binding of insulator proteins dCTCF and Su(Hw) predict TAD boundaries much worse than the active chromatin marks (in the minimal case, H3K4me3 and total RNA) do. Moreover, inter-TADs correspond to decompacted interbands of polytene chromosomes, whereas TADs mostly correspond to densely packed bands. Collectively, our results suggest that TADs are condensed chromatin domains depleted in active chromatin marks, separated by regions of active chromatin that cannot be organized into compact structures, possibly due to high levels of histone acetylation. Finally, we test this hypothesis by polymer simulations, and find that TAD partitioning can be explained by different modes of inter-nucleosomal interactions for active and inactive chromatin. Hi-C experiments, PolyA+ RNA profiling and mapping of chromosomal rearrangements in four Drosophila melanogaster cell lines.
2015-10-26 | E-GEOD-69013 | biostudies-arrayexpress
Project description:Chromosomes of metazoan organisms are partitioned in the interphase nucleus into discrete topologically associating domains (TADs). Borders between TADs are preferentially formed in regions containing high density of active genes and clusters of architectural protein binding sites. Transcription of most genes is turned off during the heat shock response in Drosophila. Here we show that temperature stress induces relocalization of architectural proteins from TAD borders to inside TADs, and this is accompanied by a dramatic rearrangement in the 3D organization of the nucleus. TAD border strength declines, allowing for an increase in long-distance inter-TAD interactions. Similar but quantitatively weaker effects are observed upon inhibition of transcription or depletion of individual architectural proteins. New heat shock-induced inter-TAD interactions result in increased contacts among enhancers and promoters of silenced genes, which recruit Pc and form Pc bodies at the nucleolus. These results suggest that the TAD organization of metazoan genomes is plastic and can be quickly reconfigured to allow new interactions between distant sequences.
2015-02-24 | GSE63515 | GEO
Project description:Chromosomes of metazoan organisms are partitioned in the interphase nucleus into discrete topologically associating domains (TADs). Borders between TADs are preferentially formed in regions containing high density of active genes and clusters of architectural protein binding sites. Transcription of most genes is turned off during the heat shock response in Drosophila. Here we show that temperature stress induces relocalization of architectural proteins from TAD borders to inside TADs, and this is accompanied by a dramatic rearrangement in the 3D organization of the nucleus. TAD border strength declines, allowing for an increase in long-distance inter-TAD interactions. Similar but quantitatively weaker effects are observed upon inhibition of transcription or depletion of individual architectural proteins. New heat shock-induced inter-TAD interactions result in increased contacts among enhancers and promoters of silenced genes, which recruit Pc and form Pc bodies at the nucleolus. These results suggest that the TAD organization of metazoan genomes is plastic and can be quickly reconfigured to allow new interactions between distant sequences.
2015-02-24 | GSE62904 | GEO
Project description:Topologically associating domains (TADs) are widely recognized as fundamental elements of the 3D structure of the eukaryotic genome. However, while the structural importance of the insulator protein CTCF together with cohesin at TAD borders in mammalian cells is well established, the absence of such co-localization at most TAD borders in recent Hi-C studies of D. melanogaster is enigmatic, raising the possibility that these TAD border elements are not generally conserved among metazoans. Using in situ Hi-C with sub-kb resolution, we show that the genome of D. melanogaster is almost completely partitioned into more than 4,000 TADs (median size, 13 kb), nearly 7-fold more than previously identified. The overwhelming majority of these TADs are demarcated by pairs of Drosophila-specific insulator proteins, BEAF-32/CP190 or BEAF-32/Chromator, indicating that these proteins may play an analogous role in Drosophila as that of the CTCF/cohesin pair in mammals. Moreover, we find that previously identified TADs enriched for inactive chromatin are predominantly assembled from the higher-level interactions between smaller TADs. In contrast, the closely-spaced small TADs in regions previously thought to be unstructured “inter-TADs” are organized in an open configuration with far fewer TAD-TAD interactions. Such structures can also be identified in some “inter-TAD” regions of the mammalian genome, suggesting that larger assemblages of small self-interacting TADs separated by a “burst” of adjacent small, weakly interacting TADs may be a conserved, basic characteristic of the higher order folding of the metazoan genome.
2017-11-22 | GSE101317 | GEO
Project description:The DNA in humans and many animals is compartmentalised in topologically associating domains (TADs). In Drosophila, several architectural proteins are enriched at TAD borders, but we are still missing evidence that these proteins have a functional role in TAD maintenance. Here, we show that depletion of BEAF-32, Cp190 and Chro leads to changes in TAD organisation and chromatin loops. Their depletion affects mainly TAD borders in heterochromatin, while euchromatin TAD borders are resilient to these mutants. Furthermore, transcriptomic data identified thousands of genes displaying differential expression in these mutants and that majority of differentially expressed genes are in TADs that are reorganised. In contrast, we observed a lower effect on gene expression by the loss of chromatin loops. Our work identified for the first time a functional role for architectural proteins at TAD borders in Drosophila and a strong link between TAD reorganisation and changes in gene expression.
2022-02-07 | GSE147059 | GEO