Integration of 3D genome topology and local chromatin features uncovers enhancers underlying craniofacial-specific cartilage defects.

ABSTRACT: Aberrations in tissue-specific enhancers underlie many developmental defects. Disrupting a noncoding region distal from the human SOX9 gene causes the Pierre Robin sequence (PRS) characterized by the undersized lower jaw. Such a craniofacial-specific defect has been previously linked to enhancers transiently active in cranial neural crest cells (CNCCs). We demonstrate that the PRS region also strongly regulates Sox9 in CNCC-derived Meckel's cartilage (MC), but not in limb cartilages, even after decommissioning of CNCC enhancers. Such an MC-specific regulatory effect correlates with the MC-specific chromatin contacts between the PRS region and Sox9, highlighting the importance of lineage-dependent chromatin topology in instructing enhancer usage. By integrating the enha

SUBMITTER: Chen Q 

PROVIDER: S-EPMC9683718 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature