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Gene Density, Transcription and Insulators Contribute to the Partition of the Drosophila Genome into Physical Domains (Hi-C analysis of Drosophila melanogaster Kc167 genome)

ABSTRACT: The mechanisms responsible for the establishment of physical domains in metazoan chromosomes are poorly understood. Here we find that physical domains in Drosophila chromosomes are demarcated at regions of active transcription and high gene density that are enriched for transcription factors and specific combinations of insulator proteins. Physical domains contain different types of chromatin defined by the presence of specific proteins and epigenetic marks, with active chromatin preferentially located at the borders and silenced chromatin in the interior. Domain boundaries participate in long-range interactions that may contribute to the clustering of regions of active or silenced chromatin in the nucleus. Analysis of transgenes suggests that chromatin is more accessible and permissive to transcription at the borders than inside domains, independent of the presence of active or silencing histone modifications. These results suggest that the higher-order physical organization of chromatin may impose an additional level of regulation over classical epigenetic marks.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE38468 | GEO | 2012/10/04

SECONDARY ACCESSION(S): PRJNA167935

REPOSITORIES: GEO

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Gene Density, Transcription and Insulators Contribute to the Partition of the Drosophila Genome into Physical Domains (Hi-C analysis of Drosophila melanogaster Kc167 genome)

Project description:The mechanisms responsible for the establishment of physical domains in metazoan chromosomes are poorly understood. Here we find that physical domains in Drosophila chromosomes are demarcated at regions of active transcription and high gene density that are enriched for transcription factors and specific combinations of insulator proteins. Physical domains contain different types of chromatin defined by the presence of specific proteins and epigenetic marks, with active chromatin preferentially located at the borders and silenced chromatin in the interior. Domain boundaries participate in long-range interactions that may contribute to the clustering of regions of active or silenced chromatin in the nucleus. Analysis of transgenes suggests that chromatin is more accessible and permissive to transcription at the borders than inside domains, independent of the presence of active or silencing histone modifications. These results suggest that the higher-order physical organization of chromatin may impose an additional level of regulation over classical epigenetic marks. We carried out Hi-C experiment using HindIII on Kc167 cells and generate two libraries separately. One library was sequenced once more as technical replicates (TR1 and TR2), the other library was sequenced as biological replicate (BR). processed files contain the following: Column 1: chromosome ID in which the first read in a pair locates Column 2: coordinate of the first read Column 3: chromosome ID in which the second read in a pair locates Column 4: coordinate of the second read

2012-10-04 | E-GEOD-38468 | biostudies-arrayexpress

Temperature Sensitive Remodeling of Fruit Fly Physical Chromosomal Domains upon Heat Shock

Project description:Metazoan chromosomes in interphase nucleus are partitioned into discrete three dimensional physical domains which confine epigenetically modified chromatin and are relative stable across different cell types even species1-4. Physical domains are segregated preferentially at DNase I hypersensitive sequences of high density of active gene and insulator proteins which are hypothesized contributing together to domain border formation3,4. However, whether physical domain structure can be maintained without insulator proteins and transcription is unknown5-8. Transcription of most genes and the insulator proteins binding can be severely impaired in heat shocked (HS) fruit fly nuclei9. Here we show that chromatin contact frequency increases within and decreases beyond ~100kb after HS respectively accompanied by repartitioning of the Drosophila chromosomes into a different array of physical domain. Prominently, domains tend to merge because borders disappeared are more than borders newly emerged which are located more frequently in repressive chromatin. In contrast to previous hypothesis1,3,4, changes in insulator proteins enrichment and RNAPII show no noticeable difference at lost or emerged borders. Our results show a metazoan genome can be quickly reconfigured as cells undergo brief physiological stress. In addition to insulator proteins and transcription, we speculate that extra trans-factors binding and various biological activities are required for the establishment and maintenance of physical domains. Moreover, we found long-range chromatin interaction network is reshaped after HS implying long-range chromatin interactions can be formed due to domain level reorganization of chromosomes despite functional relevance. We anticipate our analysis to be a starting point for more intensive experimental investigation into the elusive mechanisms behind the physical domain partition and dynamic reconfiguration of metazoan genomes.

2016-03-18 | GSE45293 | GEO

Three-dimensional folding and functional organization principles of the Drosophila genome

Project description:Chromosomes are the physical realization of genetic information and thus form the basis for its reading, hindering and propagation. Here we present a high-resolution chromosomal contact map derived from a new genome-wide chromosome conformation capture approach (a simplified version of the Hi-C method) applied to Drosophila embryonic nuclei. The data show that the entire genome is linearly partitioned into well-demarcated physical domains that overlap extensively with active and repressive epigenetic marks. Chromosomal contacts are hierarchically organized between domains. Global modeling of compaction and clustering of domains show that inactive domains are condensed and confined to their chromosomal territories, while active domains reach out of the territory to form remote intra- and inter-chromosomal contacts. One pilot sample, comprising seven paired-end Illumina GA-II lanes; one deep-sequenced sample, comprising seven paired-end Illumina HiSeq lanes

2012-01-20 | E-GEOD-34453 | biostudies-arrayexpress

Three-dimensional folding and functional organization principles of the Drosophila genome

2012-01-20 | GSE34453 | GEO

Regions of very low H3K27me3 partition the Drosophila genome into topological domains

Project description:This SuperSeries is composed of the SubSeries listed below. We have investigated boundaries of topologically associated domains (TADs) in the Drosophila genome and find that they can be identified as domains of very low H3K27me3. The genome-wide H3K27me3 profile partitions into two states; very low H3K27me3 identifies Depleted (D) domains that contain housekeeping genes and their regulators such as the histone acetyltransferase-containing NSL complex, whereas domains containing mid-to-high levels of H3K27me3 (Enriched or E domains) are associated with regulated genes, irrespective of whether they are active or inactive. The D domains correlate with the boundaries of TADs and are enriched in a subset of architectural proteins, particularly Chromator, BEAF-32, and Z4. However, rather than being clustered at the borders of these domains, these proteins bind throughout the H3K27me3-depleted regions and are much more strongly associated with the TSSs of the housekeeping genes than with the H3K27me3 domain boundaries. We suggest that the D domain chromatin state, characterised by very low H3K27me3 and established by housekeeping gene regulators, acts to separate topological domains thereby setting up the domain architecture of the genome.

2017-05-02 | GSE85504 | GEO

Regions of very low H3K27me3 partition the Drosophila genome into topological domains [HiC-seq]

Project description:We have investigated boundaries of topologically associated domains (TADs) in the Drosophila genome and find that they can be identified as domains of very low H3K27me3. The genome-wide H3K27me3 profile partitions into two states; very low H3K27me3 identifies Depleted (D) domains that contain housekeeping genes and their regulators such as the histone acetyltransferase-containing NSL complex, whereas domains containing mid-to-high levels of H3K27me3 (Enriched or E domains) are associated with regulated genes, irrespective of whether they are active or inactive. The D domains correlate with the boundaries of TADs and are enriched in a subset of architectural proteins, particularly Chromator, BEAF-32, and Z4. However, rather than being clustered at the borders of these domains, these proteins bind throughout the H3K27me3-depleted regions and are much more strongly associated with the TSSs of the housekeeping genes than with the H3K27me3 domain boundaries. We suggest that the D domain chromatin state, characterised by very low H3K27me3 and established by housekeeping gene regulators, acts to separate topological domains thereby setting up the domain architecture of the genome.

2017-05-02 | GSE85503 | GEO

ARID1A regulates condensin II distribution and chromosomal partition [HiC]

Project description:ARID1A, a subunit of the switch/sucrose non-fermentable (SWI/SNF) chromatin remodeling complex, influences gene accessibility. However, the role of ARID1A in spatial genomic organization and chromosomal interaction remains elusive. We showed that the SWI/SNF complex interacts with condensin II and they show significant overlapping distributions in enhancers. ARID1A inactivation drives redistribution of condensin II preferentially at enhancers without affecting the interaction between the SWI/SNF and condensing II complexes. ARID1A and condensin II contribute to transcriptionally inactive B compartments, while ARID1A weakens the borders of topologically associated domains. ARID1A inactivation decreases the frequency of genomic interactions over distance, but increases the intermixing of interphase small chromosomes, which was validated by three dimensional chromosome painting. These results demonstrated ARID1A spatially partitions genome and chromosomes.

2019-05-21 | GSE120059 | GEO

ARID1A regulates condensin II distribution and chromosomal partition [RNA-seq]

2019-05-21 | GSE120057 | GEO

ARID1A regulates condensin II distribution and chromosomal partition [ChIP-seq]

2019-05-21 | GSE120058 | GEO

Chromatin organization in 3D distinguishes the influences of dMes-4/NSD and Hypb/dSet2 in protecting genes from H3K27me3 silencing

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

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