A tissue-specific self-interacting chromatin domain forms independently of enhancer-promoter interactions

• DOI: 10.1038/s41467-018-06248-4
• Publication Date: 2018-09-17T11:45:50Z
• Authors: Jill M. Brown; Nigel A. Roberts; Bryony Graham; Dominic Waithe; Christoffer Lager...; Jelena M. Telenius; Sara De Ornellas; A. Marieke Oudelaar; Caroline Scott; Izabela Szczerbal; Christian Babbs; Mira T. Kassouf; Jim R. Hughes; Douglas R. Higgs; Veronica J. Buckle
• Keywords: CTCF; Chromosome conformation capture; Locus control region; Transcription

Abstract Self-interacting chromatin domains encompass genes and their cis -regulatory elements; however, the three-dimensional form a domain takes, whether this relies on enhancer–promoter interactions, processes necessary to mediate formation maintenance of such domains, remain unclear. To examine these questions, here we use combination high-resolution chromosome conformation capture, non-denaturing fluorescence in situ hybridisation super-resolution imaging study 70 kb encompassing mouse α-globin regulatory locus. We show that region forms an erythroid-specific, decompacted, self-interacting domain, delimited by frequently apposed CTCF/cohesin binding sites early terminal erythroid differentiation, does not require transcriptional elongation for structure. Formation rely interactions between major enhancers, suggesting transcription-independent mechanism establishment domain. However, absence enhancers alter internal interactions. loop therefore appears be mechanistic process occurs irrespective specific within.