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Static and Dynamic DNA Loops form AP-1-Bound Activation Hubs during Macrophage Development.

Molecular cell | 2017

The three-dimensional arrangement of the human genome comprises a complex network of structural and regulatory chromatin loops important for coordinating changes in transcription during human development. To better understand the mechanisms underlying context-specific 3D chromatin structure and transcription during cellular differentiation, we generated comprehensive in situ Hi-C maps of DNA loops in human monocytes and differentiated macrophages. We demonstrate that dynamic looping events are regulatory rather than structural in nature and uncover widespread coordination of dynamic enhancer activity at preformed and acquired DNA loops. Enhancer-bound loop formation and enhancer activation of preformed loops together form multi-loop activation hubs at key macrophage genes. Activation hubs connect 3.4 enhancers per promoter and exhibit a strong enrichment for activator protein 1 (AP-1)-binding events, suggesting that multi-loop activation hubs involving cell-type-specific transcription factors represent an important class of regulatory chromatin structures for the spatiotemporal control of transcription.

Pubmed ID: 28890333 RIS Download

Associated grants

  • Agency: NHLBI NIH HHS, United States
    Id: U01 HL130010
  • Agency: NHGRI NIH HHS, United States
    Id: UM1 HG009375
  • Agency: NHGRI NIH HHS, United States
    Id: K99 HG008662
  • Agency: NHGRI NIH HHS, United States
    Id: R00 HG008662
  • Agency: NIDDK NIH HHS, United States
    Id: F32 DK107112
  • Agency: NIH HHS, United States
    Id: DP2 OD008540
  • Agency: NHGRI NIH HHS, United States
    Id: P50 HG006193
  • Agency: NHGRI NIH HHS, United States
    Id: T32 HG000044
  • Agency: NCI NIH HHS, United States
    Id: P01 CA142538
  • Agency: NHGRI NIH HHS, United States
    Id: K22 HG000044
  • Agency: NHGRI NIH HHS, United States
    Id: U01 HG007919
  • Agency: NHGRI NIH HHS, United States
    Id: RM1 HG006193

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