title: A specific CBP/p300-dependent gene expression programme drives the metabolic remodelling in late stages of spermatogenesis.
abstract: Histone hyperacetylation is thought to drive the replacement of histones by transition proteins that occur in elongating spermatids (ElS) after a general shut down of transcription. The molecular machineries underlying this histone hyperacetylation remain still undefined. Here, we focused our attention on the role of Cbp and p300 in histone hyperacetylation and in the preceding late-gene transcriptional activity in ElS. A strategy was designed to partially deplete Cbp and p300 in ElS. These cells progressed normally through spermiogenesis and showed normal histone hyperacetylation and removal. However, a genome-wide transcriptomic analysis, performed in the round spermatids (RS) and ElS, revealed the existence of a gene regulatory circuit encompassing genes presenting high expression levels in pre-meiotic cells, undergoing a repressed state in spermatocytes and early post-meiotic cells, but becoming reactivated in ElS, just prior to the global shutdown of transcription. Interestingly, this group of genes was over-represented within the genes affected by Cbp/p300 knock down and were all involved in metabolic remodelling. This study revealed the occurrence of a tightly regulated Cbp/p300-dependent gene expression programme that drives a specific metabolic state both in progenitor spermatogenic cells and in late transcriptionally active spermatids and confirmed a special link between Cpb/p300 and cell metabolism programming previously shown in somatic cells.
authors: INSERM, U823, Institut Albert Bonniot, Université Joseph Fourier - Grenoble 1, Grenoble, France.
authors: F
authors: F
authors: Boussouar
authors: A
authors: A
authors: Goudarzi
authors: T
authors: T
authors: Buchou
authors: H
authors: H
authors: Shiota
authors: S
authors: S
authors: Barral
authors: A
authors: A
authors: Debernardi
authors: P
authors: P
authors: Guardiola
authors: P
authors: P
authors: Brindle
authors: G
authors: G
authors: Martinez
authors: C
authors: C
authors: Arnoult
authors: S
authors: S
authors: Khochbin
authors: S
authors: S
authors: Rousseaux
mesh_terms: D000107:Acetylation; D000818:Animals; D050882:CREB-Binding Protein / Q000096:biosynthesis* / Q000235:genetics*; D050881:E1A-Associated p300 Protein / Q000096:biosynthesis* / Q000235:genetics*; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D006657:Histones / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013076:Sperm Count; D013081:Sperm Motility; D013087:Spermatids / Q000166:cytology / Q000378:metabolism; D013091:Spermatogenesis / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D006657:Histones; D050882:CREB-Binding Protein; D050881:E1A-Associated p300 Protein
keywords: animal models; cell differentiation; chromatin; epigenetics; gene expression; histone modifications; immunohistochemistry; mouse; seminiferous tubules; spermatids