Genome-wide identification of estrogen receptor binding sites reveals novel estrogen-responsive pathways in adult male germ cells
| Autor: | Sharvari Deshpande, Anita Kumar, Kushaan Khambata, Sanketa Raut, Nafisa H. Balasinor |
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| Rok vydání: | 2020 |
| Předmět: |
Male
medicine.drug_class Estrogen receptor Biology Response Elements Biochemistry Rats Sprague-Dawley Biological pathway 03 medical and health sciences 0302 clinical medicine medicine Animals Estrogen Receptor beta Binding site Receptor Molecular Biology Gene 030304 developmental biology 0303 health sciences Binding Sites Genome Estrogen receptor binding Estrogen Receptor alpha Estrogens Cell Biology Rats Cell biology Germ Cells Gene Expression Regulation Estrogen 030220 oncology & carcinogenesis Chromatin immunoprecipitation hormones hormone substitutes and hormone antagonists Protein Binding |
| Zdroj: | Biochemical Journal. 477:2115-2131 |
| ISSN: | 1470-8728 0264-6021 |
| Popis: | Spermatogenesis occurs in the seminiferous epithelium that shows the presence of estrogen receptors alpha (ERα) and beta (ERβ), both of which regulate gene transcription by binding to the DNA. Estrogen responsive phases of spermatogenesis are well documented; however, the genes regulated remain inexplicit. To study the regulation of genes by estrogen in male germ cells, we performed chromatin immunoprecipitation (ChIP) sequencing for ERα and ERβ under normal physiological conditions. A total of 27 221 DNA binding regions were enriched with ERα and 20 926 binding sites with ERβ. Majority of the peaks were present in the intronic regions and located 20 kb upstream or downstream from the transcription start site (TSS). Pathway analysis of the genes enriched by ChIP-Seq showed involvement in several biological pathways. Genes involved in pathways whose role in spermatogenesis is unexplored were validated; these included prolactin, GnRH, and oxytocin signaling. All the selected genes showed the presence of estrogen response elements (EREs) in their binding region and were also found to be significantly enriched by ChIP-qPCR. Functional validation using seminiferous tubule culture after treatment with estrogen receptor subtype-specific agonist and antagonist confirmed the regulation of these genes by estrogen through its receptors. The genes involved in these pathways were also found to be regulated by the respective receptor subtypes at the testicular level in our in vivo estrogen receptor agonist rat models. Our study provides a genome-wide map of ERα and ERβ binding sites and identifies the genes regulated by them in the male germ cells under normal physiological conditions. |
| Databáze: | OpenAIRE |
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