Chromatin fiber allostery and the epigenetic code. (7th January 2015)

• Record Type: Journal Article
• Authors: Lesne, Annick; Foray, Nicolas; Cathala, Guy; Forné, Thierry; Wong, Hua; Victor, Jean-Marc
• Is Part Of: Journal of physics. Volume 27:Number 6(2015)
• Publication Date: 2015-01-07
• Subjects: epigenetics -- allosteric transition -- chromatin fiber; Condensed matter -- Periodicals; Matière condensée -- Périodiques; Vaste stoffen; Vloeistoffen; Natuurkunde; Electronic journals; Computer network resources; 530.4105
• DOI: 10.1088/0953-8984/27/6/064114
• Languages: English
• ISSNs: 0953-8984

Abstract

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 Igf 2- H 19 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.