title: Zic2 is an enhancer-binding factor required for embryonic stem cell specification.
abstract: The Zinc-finger protein of the cerebellum 2 (Zic2) is one of the vertebrate homologs of the Drosophila pair-rule gene odd-paired (opa). Our molecular and biochemical studies demonstrate that Zic2 preferentially binds to transcriptional enhancers and is required for the regulation of gene expression in embryonic stem cells. Detailed genome-wide and molecular studies reveal that Zic2 can function with Mbd3/NuRD in regulating the chromatin state and transcriptional output of genes linked to differentiation. Zic2 is required for proper differentiation of embryonic stem cells (ESCs), similar to what has been previously reported for Mbd3/NuRD. Our study identifies Zic2 as a key factor in the execution of transcriptional fine-tuning with Mbd3/NuRD in ESCs through interactions with enhancers. Our study also points to the role of the Zic family of proteins as enhancer-specific binding factors functioning in development.
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50(th) Street, Kansas City, MO 64110, USA.
authors.forename: Zhuojuan
authors.initials: Z
authors.lastname: Luo
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50(th) Street, Kansas City, MO 64110, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Gao
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50(th) Street, Kansas City, MO 64110, USA.
authors.forename: Chengqi
authors.initials: C
authors.lastname: Lin
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50(th) Street, Kansas City, MO 64110, USA; Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, 320 East Superior Street, Chicago, IL 60611, USA.
authors.forename: Edwin R
authors.initials: ER
authors.lastname: Smith
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50(th) Street, Kansas City, MO 64110, USA.
authors.forename: Stacy A
authors.initials: SA
authors.lastname: Marshall
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50(th) Street, Kansas City, MO 64110, USA.
authors.forename: Selene K
authors.initials: SK
authors.lastname: Swanson
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50(th) Street, Kansas City, MO 64110, USA.
authors.forename: Laurence
authors.initials: L
authors.lastname: Florens
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50(th) Street, Kansas City, MO 64110, USA; Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Washburn
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50(th) Street, Kansas City, MO 64110, USA; Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, 320 East Superior Street, Chicago, IL 60611, USA. Electronic address: ash@northwestern.edu.
authors.forename: Ali
authors.initials: A
authors.lastname: Shilatifard
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology; D053595:Embryonic Stem Cells / Q000166:cytology*; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000378:metabolism / Q000502:physiology; D051379:Mice; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; C492013:Mbd3 protein, mouse; D014157:Transcription Factors; C491811:Zic2 protein, mouse; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex