Chromatin fiber allostery and the epigenetic code

Lesne, Annick; Foray, Nicolas; Cathala, Guy; Forné, Thierry; Wong, Hua; Victor, Jean–Marc

doi:10.1088/0953-8984/27/6/064114

Cited by 14 publications

(15 citation statements)

References 71 publications

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“…For example, this mechanism happens on the Igf2/H19 gene locus of mouse chromosome 7 (see Ref. (Lesne et al, 2015)). The ICR located upstream of the H19 gene is methylated on the paternal allele but it remains unmethylated on the maternal allele.…”

Section: B Parental Imprintingmentioning

confidence: 99%

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The physics of epigenetics

et al. 2016

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In higher organisms, all cells share the same genome, but every cell expresses only a limited and specific set of genes that defines the cell type. During cell division, not only the genome, but also the cell type is inherited by the daughter cells. This intriguing phenomenon is achieved by a variety of processes that have been collectively termed epigenetics: the stable and inheritable changes in gene expression patterns. This article reviews the extremely rich and exquisitely multi-scale physical mechanisms that govern the biological processes behind the initiation, spreading and inheritance of epigenetic states. These include not only the changes in the molecular properties associated with the chemical modifications of DNA and histone proteins, such as methylation and acetylation, but also less conventional changes, typically in the the physics that governs the three-dimensional organization of the genome in cell nuclei. Strikingly, to achieve stability and heritability of epigenetic states, cells take advantage of many different physical principles, such as the universal behavior of polymers and copolymers, the general features of dynamical systems, and the electrostatic and mechanical properties related to chemical modifications of DNA and histones. By putting the complex biological literature under this new light, the emerging picture is that a limited set of general physical rules play a key role in initiating, shaping and transmitting this crucial "epigenetic landscape". This new perspective not only allows to rationalize the normal cellular functions, but also helps to understand the emergence of pathological states, in which the epigenetic landscape becomes dysfunctional.

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Section: B Parental Imprintingmentioning

confidence: 99%

“…This mechanism relies on DNA allostery, i.e. the change of DNA affinity to some transcription factors that is induced by supercoiling (Lesne et al, 2015).…”

Section: Non-coding Rna and Micrornamentioning

confidence: 99%

The physics of epigenetics

et al. 2016

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“…The understanding of the functional role of the 3D genome organization triggers an increasing interest in noncoding da-SNPs, whose effect on gene regulation is mediated by a change in chromatin 3D organization [7]. Such a scenario represents an instance of chromatin allostery, where the chromatin itself behave as an allosteric object [53]; here the allosteric transition would be triggered by the SNP and the effector would be some event necessary for transcription, e.g. TF binding or the formation of a promoter-enhancer loop [54].…”

Section: Architectural Snpsmentioning

confidence: 99%

Genome supranucleosomal organization and genetic susceptibility to diseases

Jablonski

Fretter

Carron

et al. 2017

AIP Conference Proceedings

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The notion of disease-associated single-nucleotide polymorphisms (da-SNP), as determined in genome-wide association studies (GWAS), is relevant for many complex pathologies, including cancers. It appeared that da-SNPs are not only markers of causal genetic variation but may contribute to the disease development through an influence on gene expression levels. We argue that understanding this possible functional role of da-SNPs requires to consider their embedding in the tridimensional (3D) multi-scale organization of the human genome. We then focus on the potential impact of da-SNPs on chromatin loops and recently observed topologically associating domains (TADs). We show that for some diseases and cancer types, da-SNPs are over-represented in the borders of these topological domains, in a way that cannot be explained by an increased exon density. This analysis of the distribution of da-SNPs within the 3D genome organization suggests candidate loci for further experimental investigation of the mechanisms underlying genetic susceptibility to diseases, in particular cancer. Recently developed techniques of chromosome conformation capture combine chemical crosslinking and sequencing to identify genomic loci contacting each other in vivo. They have shown that the mammalian genome displays three main architectural features at the large-scale level (supranucleosomal level, beyond the kb scale), nested in a hierarchical way (Figure 2): chromatin loops, topologically associating domains (TADs) of larger size exhibiting more internal contacts than contacts between domains [34, 35], and a segregation in active and inactive compartments [36].

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“…For example, the writer enzyme Euchromatic histone methyltransferase-1 (EHMT1) catalyzes histone 3 lysine 9 (H3K9) mono-and dimethylation, but not trimethylation (Tachibana et al, 2005). The combinatorial nature of histone PTMs impact on gene expression has been postulated to generate a histone code which cells use as an ''epigenetic ''memory" of previous transcriptional states, yet this model is still under debate (Comoglio & Paro, 2014;de Pretis & Pelizzola, 2014;Lesne et al, 2015;Rando, 2012).…”

Section: Introductionmentioning

confidence: 99%