title: Chromatin fiber allostery and the epigenetic code.
abstract: The notion of allostery introduced for proteins about fifty years ago has been extended since then to DNA allostery, where a locally triggered DNA structural transition remotely controls other DNA-binding events. We further extend this notion and propose that chromatin fiber allosteric transitions, induced by histone-tail covalent modifications, may play a key role in transcriptional regulation. We present an integrated scenario articulating allosteric mechanisms at different scales: allosteric transitions of the condensed chromatin fiber induced by histone-tail acetylation modify the mechanical constraints experienced by the embedded DNA, thus possibly controlling DNA-binding of allosteric transcription factors or further allosteric mechanisms at the linker DNA level. At a higher scale, different epigenetic constraints delineate different statistically dominant subsets of accessible chromatin fiber conformations, which each favors the assembly of dedicated regulatory complexes, as detailed on the emblematic example of the mouse Igf2-H19 gene locus and its parental imprinting. This physical view offers a mechanistic and spatially structured explanation of the observed correlation between transcriptional activity and histone modifications. The evolutionary origin of allosteric control supports to speak of an 'epigenetic code', by which events involved in transcriptional regulation are encoded in histone modifications in a context-dependent way.
authors.affiliation: Laboratoire de Physique Théorique de la Matière Condensée, CNRS UMR 7600, UPMC Université Paris 06, Sorbonne Universités, F-75005, Paris, France. Institut de Génétique Moléculaire de Montpellier, CNRS UMR 5535, Université de Montpellier, F-34293, Montpellier, France. CNRS GDR 3536, UPMC Université Paris 06, F-75005, Paris, France.
authors.forename: Annick
authors.initials: A
authors.lastname: Lesne
authors.forename: Nicolas
authors.initials: N
authors.lastname: Foray
authors.forename: Guy
authors.initials: G
authors.lastname: Cathala
authors.forename: Thierry
authors.initials: T
authors.lastname: Forné
authors.forename: Hua
authors.initials: H
authors.lastname: Wong
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Victor
mesh_terms: D000107:Acetylation; D000494:Allosteric Regulation; D000818:Animals; D002843:Chromatin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D006657:Histones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D051379:Mice; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D006657:Histones; C513121:IGF2 protein, mouse; D007335:Insulin-Like Growth Factor II; D004247:DNA