A specific CBP/p300-dependent gene expression program drives the metabolic remodelling in late stages of spermatogenesis.

ABSTRACT: Histone hyperacetylation is thought to drive the replacement of histones by transition proteins that occurs in elongating spermatids 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 elongating spermatids. A strategy was designed to partially deplete Cbp and p300 in elongating spermatids. These cells progressed normally through spermiogenesis and showed normal histone hyperacetylation and removal. However, a genome-wide transcriptomic analysis, performed in the round and elongating spermatids, 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 elongating spermatids, just prior to the global shut-down 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 program 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. Total RNA were obtained from post meiotic male germ cells (round spermatids and condensing spermatids) of adult mice either wild-type or with a double knock down of Cbp/P300 in post-meiotic cells. In each experiments, 6 replicates of each genotype and cell type were used.

ORGANISM(S): Mus musculus

SUBMITTER: Sophie Rousseaux 

PROVIDER: E-GEOD-55767 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress