2018 December | M. Jordan Rowley and Victor G. Corces
The 3D organization of the genome is hierarchically structured into compartments and domains, with compartments defined by chromatin state and TADs (topologically associated domains) formed by interactions between transcriptional states. CTCF and cohesin play key roles in forming loops and maintaining chromatin structure. Recent studies suggest that compartments and CTCF loops are interdependent, with transcriptional states influencing chromatin organization and vice versa. Hi-C data reveal that compartments are smaller than previously thought, and that CTCF loops are formed through cohesin-mediated extrusion. These loops can be stable or dynamic, depending on the presence of CTCF sites and transcriptional activity. Compartmental domains are smaller than TADs and are found in many organisms, including mammals, Drosophila, and plants. Transcription influences the formation of these domains, as evidenced by experiments showing that transcription inhibition reduces compartmental domain size. However, the exact role of transcription in domain formation remains unclear, as proteins involved in transcription may also contribute. CTCF loops are formed through cohesin-mediated extrusion, and their size is influenced by the duration of cohesin's extrusion activity. The extrusion process is likely rapid, with rates estimated at 375-850 bp/s. Cohesin may also be pushed by transcription factors like RNAPII, which could influence chromatin organization. CTCF loops and compartments are functionally distinct, with CTCF playing a role in enhancer-promoter interactions and compartmental domain segregation. Depletion of CTCF or cohesin leads to changes in gene expression, with some effects being more pronounced than others. The interplay between transcription, cohesin, and CTCF is complex, and further research is needed to fully understand the mechanisms underlying 3D genome organization and its relationship to gene regulation.The 3D organization of the genome is hierarchically structured into compartments and domains, with compartments defined by chromatin state and TADs (topologically associated domains) formed by interactions between transcriptional states. CTCF and cohesin play key roles in forming loops and maintaining chromatin structure. Recent studies suggest that compartments and CTCF loops are interdependent, with transcriptional states influencing chromatin organization and vice versa. Hi-C data reveal that compartments are smaller than previously thought, and that CTCF loops are formed through cohesin-mediated extrusion. These loops can be stable or dynamic, depending on the presence of CTCF sites and transcriptional activity. Compartmental domains are smaller than TADs and are found in many organisms, including mammals, Drosophila, and plants. Transcription influences the formation of these domains, as evidenced by experiments showing that transcription inhibition reduces compartmental domain size. However, the exact role of transcription in domain formation remains unclear, as proteins involved in transcription may also contribute. CTCF loops are formed through cohesin-mediated extrusion, and their size is influenced by the duration of cohesin's extrusion activity. The extrusion process is likely rapid, with rates estimated at 375-850 bp/s. Cohesin may also be pushed by transcription factors like RNAPII, which could influence chromatin organization. CTCF loops and compartments are functionally distinct, with CTCF playing a role in enhancer-promoter interactions and compartmental domain segregation. Depletion of CTCF or cohesin leads to changes in gene expression, with some effects being more pronounced than others. The interplay between transcription, cohesin, and CTCF is complex, and further research is needed to fully understand the mechanisms underlying 3D genome organization and its relationship to gene regulation.