title: ZNF143 provides sequence specificity to secure chromatin interactions at gene promoters.
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.
authors: The Princess Margaret Cancer Centre-University Health Network, Toronto, M5G 1L7, Ontario, Canada.|Department of Medical Biophysics, University of Toronto, Toronto, M5G 1L7, Ontario, Canada.
authors: Swneke D
authors: SD
authors: Bailey
authors: Department of Genetics, Norris Cotton Cancer Center, Dartmouth Medical School, Lebanon, 03755, New Hampshire, USA.|Present address: Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
authors: Xiaoyang
authors: X
authors: Zhang
authors: Department of Genetics, Norris Cotton Cancer Center, Dartmouth Medical School, Lebanon, 03755, New Hampshire, USA.
authors: Kinjal
authors: K
authors: Desai
authors: Bioinformatics and Computational Genomics Laboratory, Institut de Recherches Cliniques de Montréal (IRCM), Montreal, H2W 1R7, Quebec, Canada.
authors: Malika
authors: M
authors: Aid
authors: Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, 44106, Ohio, USA.
authors: Olivia
authors: O
authors: Corradin
authors: The Princess Margaret Cancer Centre-University Health Network, Toronto, M5G 1L7, Ontario, Canada.|Present address: The Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02139, USA.
authors: Richard
authors: R
authors: Cowper-Sal Lari
authors: Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, 44106, Ohio, USA.|Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, 44106, Ohio, USA.|Present address: Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts 02142, USA.
authors: Batool
authors: B
authors: Akhtar-Zaidi
authors: Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, 44106, Ohio, USA.|Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, 44106, Ohio, USA.
authors: Peter C
authors: PC
authors: Scacheri
authors: The Princess Margaret Cancer Centre-University Health Network, Toronto, M5G 1L7, Ontario, Canada.|Department of Medical Biophysics, University of Toronto, Toronto, M5G 1L7, Ontario, Canada.|Bioinformatics and Computational Genomics Laboratory, Institut de Recherches Cliniques de Montréal (IRCM), Montreal, H2W 1R7, Quebec, Canada.
authors: Benjamin
authors: B
authors: Haibe-Kains
authors: The Princess Margaret Cancer Centre-University Health Network, Toronto, M5G 1L7, Ontario, Canada. mlupien@uhnres.utoronto.ca.|Department of Medical Biophysics, University of Toronto, Toronto, M5G 1L7, Ontario, Canada. mlupien@uhnres.utoronto.ca.|Ontario Institute for Cancer Research, Toronto, M5G 1L7, Ontario, Canada. mlupien@uhnres.utoronto.ca.
authors: Mathieu
authors: M
authors: Lupien
mesh_terms: D001665:Binding Sites; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
chemical_list: D002843:Chromatin; D015534:Trans-Activators; C114253:ZNF143 protein, human
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