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Background  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.    Methods  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, αT1–1 (progenitor, expressing  Cga ), αT3–1 (immature, expressing  Cga  and  Gnrhr ), and LβT2 (mature, expressing  Cga ,  Gnrhr ,  Lhb , and  Fshb ), to assess changes in chromatin status and transcription factor access of gonadotrope-specific genes.    Results  We found the common mRNA α-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 αT3–1 and LβT2 cells.  Lhb  begins to open in LβT2 cells and was further opened by activin treatment. Histone H3 modifications associated with active chromatin were high on  Gnrhr  in αT3–1 and LβT2, and  Lhb  in LβT2 cells, while H3 modifications associated with repressed chromatin were low on  Gnrhr ,  Lhb,  and  Fshb  in LβT2 cells. Finally, chromatin status correlates with the progressive access of LHX3 to  Cga  and  Gnrhr , followed by PITX1 binding to the  Lhb  promoter.    Conclusion  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.

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