The dynamic interplay of chromatin modifying factors and DNA-bound transcription factors in the regulation of mouse gonadotropin genes via multiple signaling pathways

Abstract

The regulation of follicle stimulating hormone I?-subunit (FSHI?) and Luteinizing hormone I?-subunit (LHI?) genes, by histone deacetylases (HDACs) and acetyltransferases (HATs) was investigated. These genes were found to be repressed by HDAC-mediated nucleosomal-histone hypoacetylation. Chromatin immunoprecipitation (ChIP) analysis showed that HDAC1 and HDAC7 are associated to the FSHI? gene promoter, but following hormonal stimulations, these HDACs are removed. Moreover, HATs CBP, Tip60, GCN5 and pCAF were also shown to be involved in the gonadotropin gene regulation. Tip60 and GCN5 were found to be recruited to the FSHI? gene promoter following gonadotropin releasing hormone (GnRH) treatment, by estrogen receptor (ER)-I? and c-Fos. The recruitment of Tip60 to the estrogen-stimulated promoter is demonstrated to be through interactions with liganded ERI?. In addition, Smad4 is shown to corepress the GnRH- and estrogen-induced signaling pathways by interacting with ERI? and consequently regulating HAT-HDAC exchanges on the promoter.