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Pioneer Factors in Animals and Plants-Colonizing Chromatin for Gene Regulation Xuelei Lai, Leonie Verhage, Véronique Hugouvieux, Chloe Zubieta

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Pioneer Factors in Animals and Plants-Colonizing Chromatin for Gene Regulation Xuelei Lai, Leonie Verhage, Véronique Hugouvieux, Chloe Zubieta Pioneer Factors in Animals and Plants-Colonizing Chromatin for Gene Regulation Xuelei Lai, Leonie Verhage, Véronique Hugouvieux, Chloe Zubieta To cite this version: Xuelei Lai, Leonie Verhage, Véronique Hugouvieux, Chloe Zubieta. Pioneer Factors in Animals and Plants-Colonizing Chromatin for Gene Regulation. Molecules, MDPI, 2018, 23 (8), pp.1914. 10.3390/molecules23081914. hal-01985175 HAL Id: hal-01985175 https://hal.archives-ouvertes.fr/hal-01985175 Submitted on 26 May 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Distributed under a Creative Commons Attribution| 4.0 International License molecules Review Pioneer Factors in Animals and Plants—Colonizing Chromatin for Gene Regulation Xuelei Lai †, Leonie Verhage † ID , Veronique Hugouvieux and Chloe Zubieta * Laboratoire de Physiologie Cellulaire et Végétale, CNRS, Univ. Grenoble Alpes, CEA, INRA, BIG, 38000 Grenoble, France; [email protected] (X.L.); [email protected] (L.V.); [email protected] (V.H.) * Correspondence: [email protected]; Tel.: +33-043-878-0654 † These two authors contributed equally to this work. Received: 9 July 2018; Accepted: 28 July 2018; Published: 31 July 2018 Abstract: Unlike most transcription factors (TF), pioneer TFs have a specialized role in binding closed regions of chromatin and initiating the subsequent opening of these regions. Thus, pioneer TFs are key factors in gene regulation with critical roles in developmental transitions, including organ biogenesis, tissue development, and cellular differentiation. These developmental events involve some major reprogramming of gene expression patterns, specifically the opening and closing of distinct chromatin regions. Here, we discuss how pioneer TFs are identified using biochemical and genome-wide techniques. What is known about pioneer TFs from animals and plants is reviewed, with a focus on the strategies used by pioneer factors in different organisms. Finally, the different molecular mechanisms pioneer factors used are discussed, highlighting the roles that tertiary and quaternary structures play in nucleosome-compatible DNA-binding. Keywords: transcription factor; pioneer activity; cell fate transition; chromatin accessibility 1. Introduction Transcription factors (TFs) are DNA-binding proteins that read genomic information to control gene expression in all organisms [1–5]. They achieve this by binding to their cognate DNA motif in gene regulatory regions, leading to either transcriptional activation or repression depending on whether transcription machineries are recruited or excluded. In prokaryotes, TFs recognize their DNA motifs with high specificity and affinity, suggesting that DNA sequence is the determining factor in TF function and gene regulation [6]. In contrast, TFs in higher eukaryotes often interact with other TFs in a combinatorial manner to ensure specificity and affinity [7]. By further recruiting ternary factors, such as epigenetic factors or other transcriptional machineries, eukaryotic TFs are able to establish robust temporal and spatial gene expression in response to environmental or cellular conditions and at different developmental stages. Compared to prokaryotic TFs, eukaryotic TFs confront another hurdle—namely, the complex structure of chromatin in which genomic DNA is wrapped around histone proteins to form nucleosomes, which is then further compacted to form higher-order structures [8]. Histone proteins can compete with TFs for DNA-binding, therefore limiting access to transcription factor binding sites (TFBS) [9]. This chromatin barrier therefore poses a significant challenge to the establishment of new gene regulatory networks, which is required, for example, during developmental phase transitions or organ specification. To overcome such obstacles, eukaryotes have evolved a unique set of TFs that are able to bind to their cognate motifs even when nucleosomes are present, subsequently priming the region for access by other DNA-interacting or modifying proteins. Collectively, these TFs are called pioneer factors (Figure1). Molecules 2018, 23, 1914; doi:10.3390/molecules23081914 www.mdpi.com/journal/molecules Molecules 2018, 23, 1914 2 of 22 Molecules 2018, 23, 1914 2 of 22 The pioneer factor concept originated from in vivo footprinting studies, where researchers The pioneer factor concept originated from in vivo footprinting studies, where researchers sought to determine which TFs were the first ones to bind a tissue-specific enhancer during sought to determine which TFs were the first ones to bind a tissue-specific enhancer during embryonic development [10,11]. Two TFs that are important for endoderm development, FOXA1 and embryonic development [10,11]. Two TFs that are important for endoderm development, FOXA1 and GATA4, were characterized as ‘pioneer factors’. Both have been shown to be able to engage silent GATA4, were characterized as ‘pioneer factors’. Both have been shown to be able to engage silent heterochromatin,heterochromatin while, while endowing endowing these these regions regions withwith the competence for for gene gene expression expression by by allowing allowing non-pioneernon-pioneer TFs TFs to to bind bind in in the the ‘pioneered ‘pioneered sites’ sites’ [[12]12].. Further inin vitro vitro biochemicalbiochemical studies studies have have shown shown thatthat recombinant recombinant FOXA1 FOXA1 and and GATA4 GATA4 are are ableable toto bindbind compacted chromatin chromatin and and to to open open the the local local nucleosome-richnucleosome-rich domains, domains, even even in in the the absence absence of ATP-dependentof ATP-dependent chromatin chromatin remodeling remodeling enzymes enzymes [13 ]. Several[13]. Several additional additional pioneer pioneer factors factors from different from different organisms organisms have been have identified been identified in the lastin the two last decades two (Tablesdecades1 and (Table2). Ins 1 this and review, 2). In this we review, address we how address pioneer how TFs pioneer are identified TFs are identified experimentally, experimentally, through thethrough common the and common distinct and features distinct of features pioneer of TFs pioneer from TFs animals from andanimals plants and and plant thes strategiesand the strategies by which pioneerby which TFs pioneer bind and TFs open bind chromatin. and open chromatin. Additional Additional reviews ofreviews pioneer of TFs,pioneer focusing TFs, focusing on different on aspectsdifferent of their aspects activity, of their can activity be found, can elsewherebe found elsewhere for further for informationfurther information on these on key these players key players in gene regulationin gene regulation [14–22]. [14–22]. FigureFigure 1. Activity1. Activity of of pioneer pioneer transcription transcription factors.factors. Pioneer factors bind bind nucleosomal nucleosomal DNA DNA an andd open open closedclosed chromatin chromatin regions, regions, e.g., e.g. by, by displacing displacing nucleosomes,nucleosomes, so that non non-pioneer-pioneer transcription transcription factors factors can can bindbind and and regulate regulate gene gene expression. expression. In In some some cases,cases, pioneerpioneer factors promote promote epigenetic epigenetic marks marks deposition deposition andand render render the the ‘pioneered ‘pioneered sites’ sites’ inin anan active state state for for a alonger longer period period of oftime time (Table (Tabless 1 and1 and 2).2 ). 2. Identification2. Identification of of Pioneer Pioneer Factors—Biochemical Factors—Biochemical andand Genome-WideGenome-Wide Studies Studies 2.1.2.1. Electrophoretic Electrophoretic Mobility Mobility Shift Shift Assays Assays PioneerPioneer factors factors were were originally originally identifiedidentified asas master regulators regulators of of cell cell fa fatete and and their their ability ability to to reprogramreprogram cell cell fate fate has has been been investigated investigated atat thethe molecularmolecular level. The The extensive extensive reprogramming reprogramming of of gene regulatory networks triggered by pioneer factors requires the opening and/or closing of gene regulatory networks triggered by pioneer factors requires the opening and/or closing of different different chromatin regions and the binding of nucleosomal DNA (Figure 1). Indeed, the ability to chromatin regions and the binding of nucleosomal DNA (Figure1). Indeed, the ability to target target a TFBS within a nucleosome has been a defining characteristic for pioneer factors. The a TFBS within a nucleosome has been a defining characteristic for pioneer factors. The canonical canonical examples are FOXA1 and GATA4 pioneer factors, which were shown to be capable of examples are FOXA1 and GATA4 pioneer factors, which were shown to be capable of binding to in vitro binding to in vitro reconstituted nucleosomes that contain their TFBSs by electrophoretic mobility reconstitutedshift assays nucleosomes(EMSA). In these that experiments, contain their various TFBSs byliver electrophoretic-specific TFs were mobility
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