Nucleosome mapping across the CFTR locus identifies novel regulatory factors

Erbay Yigit, Jared M. Bischof, Zhaolin Zhang, Christopher J. Ott, Jenny L. Kerschner, Shih Hsing Leir, Elsy Buitrago-Delgado, Quanwei Zhang, Ji Ping Z. Wang, Jonathan Widom, Ann Harris

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Nucleosome positioning on the chromatin strand plays a critical role in regulating accessibility of DNA to transcription factors and chromatin modifying enzymes. Hence, detailed information on nucleosome depletion or movement at cis-acting regulatory elements has the potential to identify predicted binding sites for trans-acting factors. Using a novel method based on enrichment of mononucleosomal DNA by bacterial artificial chromosome hybridization, we mapped nucleosome positions by deep sequencing across 250 kb, encompassing the cystic fibrosis transmembrane conductance regulator (CFTR) gene. CFTR shows tight tissue-specific regulation of expression, which is largely determined by cis-regulatory elements that lie outside the gene promoter. Although multiple elements are known, the repertoire of transcription factors that interact with these sites to activate or repress CFTR expression remains incomplete. Here, we show that specific nucleosome depletion corresponds to well-characterized binding sites for known trans-acting factors, including hepatocyte nuclear factor 1, Forkhead box A1 and CCCTCbinding factor. Moreover, the cell-type selective nucleosome positioning is effective in predicting binding sites for novel interacting factors, such as BAF155. Finally, we identify transcription factor binding sites that are overrepresented in regions where nucleosomes are depleted in a cell-specific manner. This approach recognizes the glucocorticoid receptor as a novel trans-acting factor that regulates CFTR expression in vivo.

Original languageEnglish (US)
Pages (from-to)2857-2868
Number of pages12
JournalNucleic acids research
Volume41
Issue number5
DOIs
Publication statusPublished - Mar 1 2013
Externally publishedYes

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ASJC Scopus subject areas

  • Genetics

Cite this

Yigit, E., Bischof, J. M., Zhang, Z., Ott, C. J., Kerschner, J. L., Leir, S. H., ... Harris, A. (2013). Nucleosome mapping across the CFTR locus identifies novel regulatory factors. Nucleic acids research, 41(5), 2857-2868. https://doi.org/10.1093/nar/gks1462