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Genome-wide analysis reveals positional-nucleosome-oriented binding pattern of pioneer factor FOXA1.

Publication ,  Journal Article
Ye, Z; Chen, Z; Sunkel, B; Frietze, S; Huang, TH-M; Wang, Q; Jin, VX
Published in: Nucleic Acids Res
September 19, 2016

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.

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Published In

Nucleic Acids Res

DOI

EISSN

1362-4962

Publication Date

September 19, 2016

Volume

44

Issue

16

Start / End Page

7540 / 7554

Location

England

Related Subject Headings

  • Protein Processing, Post-Translational
  • Protein Binding
  • Nucleotide Motifs
  • Nucleosomes
  • Humans
  • Histones
  • Hepatocyte Nuclear Factor 3-alpha
  • Genome, Human
  • Developmental Biology
  • Computational Biology
 

Citation

APA
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ICMJE
MLA
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Ye, Z., Chen, Z., Sunkel, B., Frietze, S., Huang, T.-M., Wang, Q., & Jin, V. X. (2016). Genome-wide analysis reveals positional-nucleosome-oriented binding pattern of pioneer factor FOXA1. Nucleic Acids Res, 44(16), 7540–7554. https://doi.org/10.1093/nar/gkw659
Ye, Zhenqing, Zhong Chen, Benjamin Sunkel, Seth Frietze, Tim H-M Huang, Qianben Wang, and Victor X. Jin. “Genome-wide analysis reveals positional-nucleosome-oriented binding pattern of pioneer factor FOXA1.Nucleic Acids Res 44, no. 16 (September 19, 2016): 7540–54. https://doi.org/10.1093/nar/gkw659.
Ye Z, Chen Z, Sunkel B, Frietze S, Huang TH-M, Wang Q, et al. Genome-wide analysis reveals positional-nucleosome-oriented binding pattern of pioneer factor FOXA1. Nucleic Acids Res. 2016 Sep 19;44(16):7540–54.
Ye, Zhenqing, et al. “Genome-wide analysis reveals positional-nucleosome-oriented binding pattern of pioneer factor FOXA1.Nucleic Acids Res, vol. 44, no. 16, Sept. 2016, pp. 7540–54. Pubmed, doi:10.1093/nar/gkw659.
Ye Z, Chen Z, Sunkel B, Frietze S, Huang TH-M, Wang Q, Jin VX. Genome-wide analysis reveals positional-nucleosome-oriented binding pattern of pioneer factor FOXA1. Nucleic Acids Res. 2016 Sep 19;44(16):7540–7554.
Journal cover image

Published In

Nucleic Acids Res

DOI

EISSN

1362-4962

Publication Date

September 19, 2016

Volume

44

Issue

16

Start / End Page

7540 / 7554

Location

England

Related Subject Headings

  • Protein Processing, Post-Translational
  • Protein Binding
  • Nucleotide Motifs
  • Nucleosomes
  • Humans
  • Histones
  • Hepatocyte Nuclear Factor 3-alpha
  • Genome, Human
  • Developmental Biology
  • Computational Biology