Genome-wide analysis reveals positional-nucleosome-oriented binding pattern of pioneer factor FOXA1. Nucleic Acids Res 2016 Sep 19;44(16):7540-54
Date
07/28/2016Pubmed ID
27458208Pubmed Central ID
PMC5027512DOI
10.1093/nar/gkw659Scopus ID
2-s2.0-84988944828 (requires institutional sign-in at Scopus site) 11 CitationsAbstract
The compaction of nucleosomal structures creates a barrier for DNA-binding transcription factors (TFs) to access their cognate cis-regulatory elements. Pioneer factors (PFs) such as FOXA1 are able to directly access these cis-targets within compact chromatin. However, how these PFs interplay with nucleosomes remains to be elucidated, and is critical for us to understand the underlying mechanism of gene regulation. Here, we have conducted a computational analysis on a strand-specific paired-end ChIP-exo (termed as ChIP-ePENS) data of FOXA1 in LNCaP cells by our novel algorithm ePEST. We find that FOXA1 chromatin binding occurs via four distinct border modes (or footprint boundary patterns), with a preferential footprint boundary patterns relative to FOXA1 motif orientation. In addition, from this analysis three fundamental nucleotide positions (oG, oS and oH) emerged as major determinants for blocking exo-digestion and forming these four distinct border modes. By integrating histone MNase-seq data, we found an astonishingly consistent, 'well-positioned' configuration occurs between FOXA1 motifs and dyads of nucleosomes genome-wide. We further performed ChIP-seq of eight chromatin remodelers and found an increased occupancy of these remodelers on FOXA1 motifs for all four border modes (or footprint boundary patterns), indicating the full occupancy of FOXA1 complex on the three blocking sites (oG, oS and oH) likely produces an active regulatory status with well-positioned phasing for protein binding events. Together, our results suggest a positional-nucleosome-oriented accessing model for PFs seeking target motifs, in which FOXA1 can examine each underlying DNA nucleotide and is able to sense all potential motifs regardless of whether they face inward or outward from histone octamers along the DNA helix axis.
Author List
Ye Z, Chen Z, Sunkel B, Frietze S, Huang TH, Wang Q, Jin VXAuthor
Victor X. Jin PhD Professor in the Institute for Health and Equity department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AlgorithmsCell Line, Tumor
Chromatin Assembly and Disassembly
Chromatin Immunoprecipitation
Computational Biology
Genome, Human
Hepatocyte Nuclear Factor 3-alpha
Histones
Humans
Nucleosomes
Nucleotide Motifs
Protein Binding
Protein Processing, Post-Translational