Chromatin looping and organization at developmentally regulated gene loci

Abstract

Developmentally regulated genes are often controlled by distant enhancers, silencers and insulators, to implement their correct transcriptional programs. In recent years, the development of 3C and derived techniques (4C, 5C, HiC, ChIA-PET, etc.) has confirmed that chromatin looping is an important mechanism for the transfer of regulatory information in mammalian cells. At many developmentally regulated gene loci, transcriptional activation is indeed accompanied by the formation of chromatin loops between genes and distant enhancers. Similarly, dynamic looping between insulator elements and changes in local 3D organization may be observed upon variation in transcriptional activity. Chromatin looping also occurs at silent gene loci, where its function remains less understood. In lineage-committed cells, partial 3D configurations are detected at loci that are activated at later stages. However, these partial configurations usually lack promoter-enhancer loops that accompany transcriptional activation, suggesting they have structural functions. Definitive evidence for a repressive role of chromatin looping is still lacking. Chromatin loops have been reported at repressed loci but, alternatively, they may act as a distraction for active loops. Together, these mechanisms allow fine-tuning of regulatory programs, thus providing further diversity in the transcriptional control of developmentally regulated gene loci.