Nucleosome Eviction and Multiple Co-Factor Binding Predict Estrogen-Receptor-Alpha-Asociated Long-Range Interactions

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Nucleosome Eviction and Multiple Co-Factor Binding Predict Estrogen-Receptor-Alpha-Asociated Long-Range Interactions

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Title: Nucleosome Eviction and Multiple Co-Factor Binding Predict Estrogen-Receptor-Alpha-Asociated Long-Range Interactions
Author(s):
He, C.;
Wang, X.;
Zhang, Michael Q.
Date Created: 2014-04-29
Item Type: Article
Keywords: Show Keywords
Description: Includes supplementary data.
Abstract: Many enhancers regulate their target genes via long-distance interactions. High-throughput experiments like ChIA-PET have been developed to map such largely cell-type-specific interactions between cis-regulatory elements genome-widely. In this study, we integrated multiple types of data in order to reveal the general hidden patterns embedded in the ChIA-PET data. We found characteristic distance features related to promoter-promoter, enhancer-enhancer and insulator-insulator interactions. Although a protein may have many binding sites along the genome, our hypothesis is that those sites that share certain open chromatin structure can accommodate relatively larger protein complex consisting of specific regulatory and 'bridging' factors, and may be more likely to form robust long-range deoxyribonucleic acid (DNA) loops. This hypothesis was validated in the estrogen receptor alpha (ERa) ChIA-PET data. An efficient classifier was built to predict ERa-associated long-range interactions solely from the related ChIP-seq data, hence linking distal ERa-dependent enhancers to their target genes. We further applied the classifier to generate additional novel interactions, which were undetected in the original ChIA-PET paper but were validated by other independent experiments. Our work provides a new insight into the long-range chromatin interactions through deeper and integrative ChIA-PET data analysis and demonstrates DNA looping predictability from ordinary ChIP-seq data.
Publisher: Oxford University Press
ISSN: 1362-4962
Source: Nucleic Acids Research
Link to Related Resource: http://dx.doi.org/10.1093/nar/gku327
Persistent Link: http://hdl.handle.net/10735.1/4150
Bibliographic Citation: He, C., X. Wang, and M. Q. Zhang. 2014. "Nucleosome eviction and multiple co-factor binding predict estrogen-receptor-alpha-associated long-range interactions." Nucleic Acids Research 42(11): 6935-6944.
Terms of Use: CC BY-NC 3.0
©2014 The Authors
Sponsors: "National Basic Research Program of China [2012CB316503]; National Natural Science Foundation of China [91019016, 61322310, 31371341, 31361163004]; Foundation for the Author of National Excellent Doctoral Dissertation of PR China [201158]; National Institutes of Health [HG001696, ES017166 to M.Q.Z.]. Funding for open access charge: National Basic Research Program of China [2012CB316503]."

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