De la régulation du génome à la progression tumorale

Acétylation de la lysine 16 de l’histone H4

Histone H4 lysine 16 acetylation: from genome regulation to tumoral progression

Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, États-Unis

^* benoit_miotto@hms.harvard.edu

Résumé

De nombreuses modifications post-traductionnelles ont pour siège les histones, autour desquelles s’enroule l’ADN pour former le nucléosome. Comment ces modifications perturbentelles l’accès au matériel génétique ? Cet article illustre le rôle majeur d’une de ces modifications, l’acétylation de la lysine 16 de l’histone H4. Des découvertes récentes ont, en effet, souligné la place prépondérante qu’elle occupe dans des phénomènes cruciaux : la régulation de la transcription, la spécialisation fonctionnelle de la chromatine, la compaction des chromosomes et la croissance tumorale.

Abstract

The histones, that wrap the DNA to form the nucleosome core, are targeted by diverse post-translational modifications. How those modifications affect DNA accessibility and chromatin folding is a fundamental biological issue. Furthermore, tremendous amounts of data suggest that the loss of specific modifications as well as an inappropriate ectopic pattern of modifications at given loci contributes to the development of several human syndromes as well as cancers. In this review, we focus on the current knowledge of the regulation and impact of histone H4 lysine 16 acetylation on the genome. Recent discoveries highlight its crucial involvement in events such as transcription regulation, chromatin specialization, chromosome compaction and tumoral progression.