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.
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.
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.
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.
Project description:After fertilization, early embryos undergo dissolution of conventional chromatin organization including topologically associating domains (TADs)1,2. Zygotic genome activation (ZGA) then commences amid unusually slow de novo establishment of 3D chromatin architecture2. How chromatin organization is established and how it interplays with transcription in early mammalian embryos remain elusive. Here, we show that CTCF occupies chromatin throughout mouse early development. By contrast, cohesin poorly binds chromatin in 1-cell embryos, coinciding with TAD dissolution. Cohesin binding then progressively increases from 2-cell to 8-cell embryos, accompanying TAD establishment. Unexpectedly, strong “genic cohesin islands (GCIs)” emerge across gene bodies of active genes in this period. GCI genes enrich for cell identity and regulatory genes, exhibit broad H3K4me3 at promoters, and display strong binding of transcription factors and the cohesin loader NIPBL at nearby enhancers. We show that transcription is hyperactive in 2-8-cell embryos and is required for GCI formation. Conversely, induced transcription can also create GCIs. Finally, GCIs can function as insulation boundaries and form contact domains with nearby CTCF sites, promoting both the transcription levels and stability of GCI genes. These data reveal a hypertranscription state in early embryos that both shapes and is fostered by the 3D genome organization, revealing intimate interplay between chromatin structure and transcription.