The Role of TAF 4b in Regulating the Gonadotropin Gene FSHβ

TAF 4b was first discovered as a tissue-specific subunit of TFIID in human B cells. The development of infertility in TAF 4b knockdown mice revealed its role in gonadal development. Its knockdown results in an increase in FSHβ expression, and affects the expression of several regulatory proteins involved in the FSHβ regulation in the LβT2 gonadotrope cell line. However, TAF 4b is not associated with the FSHβ promoter. Thus we hypothesize that TAF 4b indirectly regulates FSHβ gene expression through regulating FSHβ inhibiting/repressor proteins, inhibin α subunit and MEF2A/2D. We showed that inhibin α is down-regulated in TAF 4b knockdown cells and its knockdown results in an increase in FSHβ expression. The association of TAF 4b to the inhibin α promoter was studied using chromatin immunoprecipitation. We also showed that TAF 4b knockdown results in a decrease in MEF2A/2D (an FSHβ repressor) but an increase in Nur77 (an FSHβ activator) protein level. We thus provide a model of an indirect repression of the FSHβ gene expression by TAF 4b through promoting the expression of the inhibitory inhibin α subunit and the expression of MEF2A/2D, which recruits corepressors and HDACs to the Nur77 gene and FSHβ gene.