tailieunhanh - Báo cáo khoa học: The role of histones in chromatin remodelling during mammalian spermiogenesis

HAND2/dHAND is a basic helix-loop-helix transcription factor expressed in the heart and neural crest derivatives during embryogenesis. Although dHAND is essential for branchial arch, cardiovascular and limb development, its target genes have not been identified. The regulatory mech-anisms of dHAND function also remain relatively unknown. Here we report that Akt/PKB, a serine/threonine protein kinase involved in cell survival, growth and differ-entiation, phosphorylates dHAND and inhibits dHAND-mediated transcription | Eur. J. Biochem. 271 3459-3469 2004 FEBS 2004 doi REVIEW ARTICLE The role of histones in chromatin remodelling during mammalian spermiogenesis Jerome Govin Cecile Caron Cecile Lestrat Sophie Rousseaux and Saadi Khochbin Laboratoire de Biologie Moléculaire et Cellulaire de la Differentiation INSERM U309 Equipe Chromatine et Expression des genes Institut Albert Bonniot Faculte de medecine La Tronche France One of the most dramatic chromatin remodelling processes takes place during mammalian spermatogenesis. Indeed during the postmeiotic maturation of male haploid germ cells or spermiogenesis histones are replaced by small basic proteins which in mammals are transition proteins and protamines. However nothing is known of the mechanisms controlling the process of histone replacement. Two hints from the literature could help to shed light on the underlying molecular events one is the massive synthesis of histone variants including testis-specific members and the second is a stage specific post-translational modification of histones. A new testis-specific histone code can therefore be generated combining both histone variants and histone post-translational modifications. This review will detail these two phenomena and discuss possible functional significance of the global chromatin alterations occurring prior to histone replacement during spermiogenesis. Keywords bromodomain chromodomain epigenetics histone chaperone histone structure. Introduction The basic unit of chromatin is the nucleosome which consists of 146 base pairs of DNA wrapped around an octamer of core histones including two molecules of H2A H2B H3 and H4 1 . A fifth histone H1 protects additional DNA fragments linking neighbouring nucleosomes 2 . The nucleosomes are also the building blocks of a complex organization of chromatin which adopts different architectures in response to specific stimuli. These include organization states going from a beads-on-a-string structure to

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