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

Jill M. Brown, Nigel A. Roberts, Bryony Graham, Dominic Waithe, Christoffer Lagerholm, Jelena M. Telenius, Sara Ornellas, A. Marieke Oudelaar, Caroline Scott, Izabela Szczerbal, Christian Babbs, Mira T. Kassouf, Jim R. Hughes, Douglas R. Higgs and Veronica J. Buckle ()
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Jill M. Brown: MRC Weatherall Institute of Molecular Medicine, Oxford University
Nigel A. Roberts: MRC Weatherall Institute of Molecular Medicine, Oxford University
Bryony Graham: MRC Weatherall Institute of Molecular Medicine, Oxford University
Dominic Waithe: MRC Weatherall Institute of Molecular Medicine
Christoffer Lagerholm: MRC Weatherall Institute of Molecular Medicine
Jelena M. Telenius: MRC Weatherall Institute of Molecular Medicine, Oxford University
Sara Ornellas: MRC Weatherall Institute of Molecular Medicine, Oxford University
A. Marieke Oudelaar: MRC Weatherall Institute of Molecular Medicine, Oxford University
Caroline Scott: MRC Weatherall Institute of Molecular Medicine, Oxford University
Izabela Szczerbal: MRC Weatherall Institute of Molecular Medicine, Oxford University
Christian Babbs: MRC Weatherall Institute of Molecular Medicine, Oxford University
Mira T. Kassouf: MRC Weatherall Institute of Molecular Medicine, Oxford University
Jim R. Hughes: MRC Weatherall Institute of Molecular Medicine, Oxford University
Douglas R. Higgs: MRC Weatherall Institute of Molecular Medicine, Oxford University
Veronica J. Buckle: MRC Weatherall Institute of Molecular Medicine, Oxford University

Nature Communications, 2018, vol. 9, issue 1, 1-15

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

Date: 2018
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DOI: 10.1038/s41467-018-06248-4

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