Similar Datasets
Project description:Fundamental features of 3D genome organization are established de novo in the early embryo, including clustering of pericentromeric regions, the folding of chromosome arms and the segregation of chromosomes into active (A-) and inactive (B-) compartments. However, the molecular mechanisms that drive de novo organization remain unknown1,2. Here, by combining chromosome conformation capture (Hi-C), chromatin immunoprecipitation with high-throughput sequencing (ChIP-seq), 3D DNA fluorescence in situ hybridization (3D DNA FISH) and polymer simulations, we show that heterochromatin protein 1a (HP1a) is essential for de novo 3D genome organization during Drosophila early development. The binding of HP1a at pericentromeric heterochromatin is required to establish clustering of pericentromeric regions. Moreover, HP1a binding within chromosome arms is responsible for overall chromosome folding and has an important role in the formation of B-compartment regions. However, depletion of HP1a does not affect the A-compartment, which suggests that a different molecular mechanism segregates active chromosome regions. Our work identifies HP1a as an epigenetic regulator that is involved in establishing the global structure of the genome in the early embryo.
| S-EPMC8116211 | biostudies-literature
Project description:The genome of the fertilized egg becomes structurally and functionally reorganized during early embryogenesis. This includes the segregation of active and inactive chromosome regions into A and B compartments, which are a fundamental feature of genome organization in both vertebrates and invertebrates. Mutually exclusive and attractive interactions within each compartment are thought to contribute to compartment formation1,2. However, the molecular nature of compartmental forces, and thus how compartments form, remain unknown. Here we show that HP1a is a major driver of compartmental segregation in Drosophila early development. Depletion of HP1a leads to an overall decrease of compartmentalization and increased intra-chromosomal interactions. Polymer modeling analysis of Hi-C data and ChIP-seq suggest that establishment of the B compartment is driven by HP1a-mediated attractive interactions. Thus, HP1 controls the establishment of higher order 3D structure during early embryogenesis.
2021-04-03 | GSE140540 | GEO
Project description:The genome of the fertilized egg becomes structurally and functionally reorganized during early embryogenesis. This includes the segregation of active and inactive chromosome regions into A and B compartments, which are a fundamental feature of genome organization in both vertebrates and invertebrates. Mutually exclusive and attractive interactions within each compartment are thought to contribute to compartment formation1,2. However, the molecular nature of compartmental forces, and thus how compartments form, remain unknown. Here we show that HP1a is a major driver of compartmental segregation in Drosophila early development. Depletion of HP1a leads to an overall decrease of compartmentalization and increased intra-chromosomal interactions. Polymer modeling analysis of Hi-C data and ChIP-seq suggest that establishment of the B compartment is driven by HP1a-mediated attractive interactions. Thus, HP1 controls the establishment of higher order 3D structure during early embryogenesis.
2021-04-03 | GSE140541 | GEO
Project description:The genome of the fertilized egg becomes structurally and functionally reorganized during early embryogenesis. This includes the segregation of active and inactive chromosome regions into A and B compartments, which are a fundamental feature of genome organization in both vertebrates and invertebrates. Mutually exclusive and attractive interactions within each compartment are thought to contribute to compartment formation1,2. However, the molecular nature of compartmental forces, and thus how compartments form, remain unknown. Here we show that HP1a is a major driver of compartmental segregation in Drosophila early development. Depletion of HP1a leads to an overall decrease of compartmentalization and increased intra-chromosomal interactions. Polymer modeling analysis of Hi-C data and ChIP-seq suggest that establishment of the B compartment is driven by HP1a-mediated attractive interactions. Thus, HP1 controls the establishment of higher order 3D structure during early embryogenesis.
2021-04-03 | GSE140539 | GEO
Project description:HP1 drives de novo 3D genome reorganization in early Drosophila embryos
| PRJNA590149 | ENA
Project description:HP1 drives de novo 3D genome reorganization in early Drosophila embryos (HiC)
| PRJNA590155 | ENA
Project description:HP1 drives de novo 3D genome reorganization in early Drosophila embryos (RNA-seq)
| PRJNA590154 | ENA
Project description:HP1 drives de novo 3D genome reorganization in early Drosophila embryos (ChIP-seq)
| PRJNA590156 | ENA
Project description:Topologically associating domains, or TADs, are functional units that organize chromosomes into 3D structures of interacting chromatin. TADs play an important role in regulating gene expression by constraining enhancer-promoter contacts and there is evidence that deletion of TAD boundaries leads to aberrant expression of neighboring genes. While the mechanisms of TAD formation have been well-studied, current knowledge on the patterns of TAD evolution across species is limited. Due to the integral role TADs play in gene regulation, their structure and organization is expected to be conserved during evolution. However, more recent research suggests that TAD structures diverge relatively rapidly. We use Hi-C chromosome conformation capture to measure evolutionary conservation of whole TADs and TAD boundary elements between D. melanogaster and D. triauraria, two early-branching species from the melanogaster species group which diverged ∼15 million years ago. We find that the majority of TADs have been reorganized since the common ancestor of D. melanogaster and D. triauraria, via a combination of chromosomal rearrangements and gain/loss of TAD boundaries. TAD reorganization between these two species is associated with a localized effect on gene expression, near the site of disruption. By separating TADs into subtypes based on their chromatin state, we find that different subtypes are evolving under different evolutionary forces. TADs enriched for broadly expressed, transcriptionally active genes are evolving rapidly, potentially due to positive selection, whereas TADs enriched for developmentally-regulated genes remain conserved, presumably due to their importance in restricting gene-regulatory element interactions. These results provide novel insight into the evolutionary dynamics of TADs and help to reconcile contradictory reports related to the evolutionary conservation of TADs and whether changes in TAD structure affect gene expression.
| S-EPMC7746282 | biostudies-literature
Project description:Polycomb-group (PcG)-mediated transcriptional repression of target genes can be delineated into two phases. First, following initial repression of target genes by gene-specific transcription factors, PcG proteins recognize the repressed state and assume control of the genes' repression. Second, once the silenced state is established, PcG proteins may maintain repression through an indefinite number of cell cycles. Little is understood about how PcG proteins initially recognize the repressed state of target genes and the steps leading to de novo establishment of PcG-mediated repression. We describe a genetic system in which a Drosophila PcG target gene, giant (gt), is ubiquitously repressed during early embryogenesis by a maternally expressed transcription factor, and show the temporal recruitment of components of three PcG protein complexes: PhoRC, PRC1 and PRC2. We show that de novo PcG recruitment follows a temporal hierarchy in which PhoRC stably localizes at the target gene at least 1 h before stable recruitment of PRC2 and concurrent trimethylation of histone H3 at lysine 27 (H3K27me3). The presence of PRC2 and increased levels of H3K27me3 are found to precede stable binding by PRC1.
| S-EPMC6288389 | biostudies-literature