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
Published in:Cell 2017-12, Vol.171 (7), p.1573-1588.e28
Main Authors: Weintraub, Abraham S., Li, Charles H., Zamudio, Alicia V., 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, Jaenisch, Rudolf, Bradner, James E., Gray, Nathanael S., Young, Richard A.
Format: Article
Language:English
Subjects:
Animals
CCCTC-Binding Factor - metabolism
chromosome structure
Embryonic Stem Cells - metabolism
Enhancer Elements, Genetic
enhancers
gene regulation
Humans
Mice
Promoter Regions, Genetic
promoters
YY1 Transcription Factor - metabolism
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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. [Display omitted] •YY1 generally occupies active enhancers and promoters across cell types•YY1 can form dimers and promote DNA interactions•Perturbation of YY1 binding disrupts enhancer-promoter looping and gene expression•YY1’s structural role accounts for diverse functions reported previously YY1 is a structural regulator of enhancer-promoter interactions and facilitates gene expression.
ISSN:0092-8674
1097-4172
DOI:10.1016/j.cell.2017.11.008