Chromatin status and transcription factor binding to gonadotropin promoters in gonadotrope cell lines.

ABSTRACT: Proper expression of key reproductive hormones from gonadotrope cells of the pituitary is required for pubertal onset and reproduction. To further our understanding of the molecular events taking place during embryonic development, leading to expression of the glycoproteins luteinizing hormone (LH) and follicle-stimulating hormone (FSH), we characterized chromatin structure changes, imparted mainly by histone modifications, in model gonadotrope cell lines.We evaluated chromatin status and gene expression profiles by chromatin immunoprecipitation assays, DNase sensitivity assay, and RNA sequencing in three developmentally staged gonadotrope cell lines, ?T1-1 (progenitor, expressing Cga), ?T3-1 (immature, expressing Cga and Gnrhr), and L?T2 (mature, expressing Cga, Gnrhr, Lhb, and Fshb), to assess changes in chromatin status and transcription factor access of gonadotrope-specific genes.We found the common mRNA ?-subunit of LH and FSH, called Cga, to have an open chromatin conformation in all three cell lines. In contrast, chromatin status of Gnrhr is open only in ?T3-1 and L?T2 cells. Lhb begins to open in L?T2 cells and was further opened by activin treatment. Histone H3 modifications associated with active chromatin were high on Gnrhr in ?T3-1 and L?T2, and Lhb in L?T2 cells, while H3 modifications associated with repressed chromatin were low on Gnrhr, Lhb, and Fshb in L?T2 cells. Finally, chromatin status correlates with the progressive access of LHX3 to Cga and Gnrhr, followed by PITX1 binding to the Lhb promoter.Our data show the gonadotrope-specific genes Cga, Gnrhr, Lhb, and Fshb are not only controlled by developmental transcription factors, but also by epigenetic mechanisms that include the modulation of chromatin structure, and histone modifications.

SUBMITTER: Xie H 

PROVIDER: S-EPMC5655979 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature