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3D-genomics (Landmarks (2012: Topological domains in mammalian genomes…

- - - - A: gene rich + higher expression + accessible chromatin + activating/repressive chromatin marks
      - B: inactive chromatin
    - - 1 kb resolution for GM12878
      - Genomes are partitioned in contact domains (180kb length)
      - Distinct patterns of histone marks in each contact domain
      - Segregation into 6 subcompartments
      - 10000 loops identified
        
        Link promoter-enhancers, correlate with gene activation and are conserved across cell types
        
        Loop anchors occur at domain boundaries
        
        Loop anchors bind CTCF
        
        CTCFs at loop anchors predominantly occur in convergent orientation
  - - - Only 15% of CTCF sites are at boundaries --> it is insufficient for boundary formation
      - TSS enriched at boundaries + Housekeeping genes
    - - Chromatin looping is enriched at cis-regulatory elements: active promoters, enhancers and CTCF binding sites. They are also enriched at repressive chromatin (H3K27me3).
      - Interactions centered on CTCF binding sites occur over longer ranges than other cis-elements
      - Enhancer and promoters form complex networks to regulate transcription
      - No alterations of megabase topological domains in IMR90 after TNF-a treatment
- - - - $$P(i,j)=f(mappability, length, GC)$$