YY1 Is a Structural Regulator of Enhancer-Promoter Loops

There is considerable evidence that chromosome structure plays important roles in gene control, but we have limited understanding of the proteins that contribute to structural interactions between gene promoters and their enhancer elements. Large DNA loops that encompass genes and their regulatory e...

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Bibliographic Details
Main Authors: Sigova, Alla A., Hannett, Nancy M., Day, Daniel S., Abraham, Brian J., Cohen, Malkiel A., Nabet, Behnam, Buckley, Dennis L., Guo, Yang Eric, Hnisz, Denes, Bradner, James E., Gray, Nathanael S., Weintraub, Abraham Selby, Li, Charles Han, Zamudio Montes de Oca, Alicia, Jaenisch, Rudolf, Young, Richard A.
Other Authors: Massachusetts Institute of Technology. Department of Biology
Format: Article
Published: Elsevier BV 2018
Online Access:http://hdl.handle.net/1721.1/119424
https://orcid.org/0000-0003-0998-9882
https://orcid.org/0000-0001-8091-6112
https://orcid.org/0000-0001-6263-2423
https://orcid.org/0000-0001-8855-8647
Description
Summary:There is considerable evidence that chromosome structure plays important roles in gene control, but we have limited understanding of the proteins that contribute to structural interactions between gene promoters and their enhancer elements. Large DNA loops that encompass genes and their regulatory elements depend on CTCF-CTCF interactions, but most enhancer-promoter interactions do not employ this structural protein. Here, we show that the ubiquitously expressed transcription factor Yin Yang 1 (YY1) contributes to enhancer-promoter structural interactions in a manner analogous to DNA interactions mediated by CTCF. YY1 binds to active enhancers and promoter-proximal elements and forms dimers that facilitate the interaction of these DNA elements. Deletion of YY1 binding sites or depletion of YY1 protein disrupts enhancer-promoter looping and gene expression. We propose that YY1-mediated enhancer-promoter interactions are a general feature of mammalian gene control. YY1 is a structural regulator of enhancer-promoter interactions and facilitates gene expression.