title: Catalytic-Independent Functions of PARP-1 Determine Sox2 Pioneer Activity at Intractable Genomic Loci.
abstract: Pioneer transcription factors (TFs) function as genomic first responders, binding to inaccessible regions of chromatin to promote enhancer formation. The mechanism by which pioneer TFs gain access to chromatin remains an important unanswered question. Here we show that PARP-1, a nucleosome-binding protein, cooperates with intrinsic properties of the pioneer TF Sox2 to facilitate its binding to intractable genomic loci in embryonic stem cells. These actions of PARP-1 occur independently of its poly(ADP-ribosyl) transferase activity. PARP-1-dependent Sox2-binding sites reside in euchromatic regions of the genome with relatively high nucleosome occupancy and low co-occupancy by other transcription factors. PARP-1 stabilizes Sox2 binding to nucleosomes at suboptimal sites through cooperative interactions on DNA. Our results define intrinsic and extrinsic features that determine Sox2 pioneer activity. The conditional pioneer activity observed with Sox2 at a subset of binding sites may be a key feature of other pioneer TFs operating at intractable genomic loci.
authors.affiliation: The Laboratory of Signaling and Gene Expression, Cecil H. and Ida Green Center for Reproductive Biology Sciences and The Division of Basic Research, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX 75390-8511, USA; Program in Genetics, Development, and Disease, Graduate School of Biomedical Sciences, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Ziying
authors.initials: Z
authors.lastname: Liu
authors.affiliation: The Laboratory of Signaling and Gene Expression, Cecil H. and Ida Green Center for Reproductive Biology Sciences and The Division of Basic Research, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, TX 75390-8511, USA; Program in Genetics, Development, and Disease, Graduate School of Biomedical Sciences, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: lee.kraus@utsouthwestern.edu.
authors.forename: W Lee
authors.initials: WL
authors.lastname: Kraus
mesh_terms: D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000201:enzymology*; D022041:Euchromatin / Q000201:enzymology* / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D056426:Genetic Loci; D006801:Humans; D051379:Mice; D009707:Nucleosomes / Q000201:enzymology* / Q000235:genetics; D039904:Pluripotent Stem Cells / Q000201:enzymology*; D000071137:Poly (ADP-Ribose) Polymerase-1 / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection
chemical_list: D022041:Euchromatin; D009707:Nucleosomes; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D004247:DNA; C499320:PARP1 protein, human; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1
keywords: PARP-1; Sox2; chromatin; embryonic stem cells; nucleosome; nucleosome rotational positioning; pioneer transcription factor; transcription