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

Reproductive Biology and Endocrinology

Research

Mary Jean Sunshine¹  Pamela L. Mellon¹  Huimin Xie¹  Cindy Ngo¹  Hanne M. Hoffmann¹  Melissa J. Brayman²  Anita K. Iyer³ 

[1] Department of Reproductive Medicine, Center for Reproductive Science and Medicine, University of California, 9500 Gilman Drive La Jolla, 92093-0674, San Diego, CA, USA;Department of Reproductive Medicine, Center for Reproductive Science and Medicine, University of California, 9500 Gilman Drive La Jolla, 92093-0674, San Diego, CA, USA;Foley and Lardner LLP, 402 West Broadway, Suite 2100, 92101, San Diego, CA, USA;Department of Reproductive Medicine, Center for Reproductive Science and Medicine, University of California, 9500 Gilman Drive La Jolla, 92093-0674, San Diego, CA, USA;Illumina Inc, 5200 Illumina Way, 92122, San Diego, CA, USA;

关键词: Epigenetic;    DNA accessibility;    Histone modification;    Gonadotrope development;    ChIP Assay;    Chromatin;   

DOI  :  10.1186/s12958-017-0304-z

 received in 2017-03-28, accepted in 2017-10-04,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundProper 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.MethodsWe 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.ResultsWe 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.ConclusionOur 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.

【 授权许可】

CC BY   
© The Author(s). 2017