ZNF143 provides sequence specificity to secure chromatin interactions at gene promoters

Swneke D. Bailey, Xiaoyang Zhang, Kinjal Desai, Malika Aid, Olivia Corradin, Richard Cowper-Sal·lari, Batool Akhtar-Zaidi, Peter C. Scacheri, Benjamin Haibe-Kains and Mathieu Lupien ()
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Swneke D. Bailey: The Princess Margaret Cancer Centre—University Health Network
Xiaoyang Zhang: Norris Cotton Cancer Center, Dartmouth Medical School
Kinjal Desai: Norris Cotton Cancer Center, Dartmouth Medical School
Malika Aid: Bioinformatics and Computational Genomics Laboratory, Institut de Recherches Cliniques de Montréal (IRCM)
Olivia Corradin: Case Western Reserve University
Richard Cowper-Sal·lari: The Princess Margaret Cancer Centre—University Health Network
Batool Akhtar-Zaidi: Case Western Reserve University
Peter C. Scacheri: Case Western Reserve University
Benjamin Haibe-Kains: The Princess Margaret Cancer Centre—University Health Network
Mathieu Lupien: The Princess Margaret Cancer Centre—University Health Network

Nature Communications, 2015, vol. 6, issue 1, 1-10

Abstract: Abstract Chromatin interactions connect distal regulatory elements to target gene promoters guiding stimulus- and lineage-specific transcription. Few factors securing chromatin interactions have so far been identified. Here, by integrating chromatin interaction maps with the large collection of transcription factor-binding profiles provided by the ENCODE project, we demonstrate that the zinc-finger protein ZNF143 preferentially occupies anchors of chromatin interactions connecting promoters with distal regulatory elements. It binds directly to promoters and associates with lineage-specific chromatin interactions and gene expression. Silencing ZNF143 or modulating its DNA-binding affinity using single-nucleotide polymorphisms (SNPs) as a surrogate of site-directed mutagenesis reveals the sequence dependency of chromatin interactions at gene promoters. We also find that chromatin interactions alone do not regulate gene expression. Together, our results identify ZNF143 as a novel chromatin-looping factor that contributes to the architectural foundation of the genome by providing sequence specificity at promoters connected with distal regulatory elements.

Date: 2015
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DOI: 10.1038/ncomms7186

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