Estrogen represses gene expression through reconfiguring chromatin structures
| Autor: | Xinghua Lu, Kevin N. Lu, Panayiotis V. Benos, Hatice U. Osmanbeyoglu, Claudia Coronnello, Steffi Oesterreich, Roger Day |
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| Rok vydání: | 2013 |
| Předmět: |
Transcription
Genetic Transcription coregulator Gene Regulation Chromatin and Epigenetics Biology Chromatin remodeling Histones 03 medical and health sciences 0302 clinical medicine Genetics Humans Computer Simulation Promoter Regions Genetic ChIA-PET Estrogen receptor beta 030304 developmental biology 0303 health sciences Pioneer factor Estrogen Receptor alpha Estrogens Promoter Chromatin Gene Expression Regulation 030220 oncology & carcinogenesis MCF-7 Cells RNA Polymerase II Estrogen receptor alpha hormones hormone substitutes and hormone antagonists Transcription Factors |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 0305-1048 |
| DOI: | 10.1093/nar/gkt586 |
| Popis: | Estrogen regulates over a thousand genes, with an equal number of them being induced or repressed. The distinct mechanisms underlying these dual transcriptional effects remain largely unknown. We derived comprehensive views of the transcription machineries assembled at estrogen-responsive genes through integrating multiple types of genomic data. In the absence of estrogen, the majority of genes formed higher-order chromatin structures, including DNA loops tethered to protein complexes involving RNA polymerase II (Pol II), estrogen receptor alpha (ERα) and ERα-pioneer factors. Genes to be ‘repressed’ by estrogen showed active transcription at promoters and throughout the gene bodies; genes to be ‘induced’ exhibited active transcription initiation at promoters, but with transcription paused in gene bodies. In the presence of estrogen, the majority of estrogen-induced genes retained the original higher-order chromatin structures, whereas most estrogen-repressed genes underwent a chromatin reconfiguration. For estrogen-induced genes, estrogen enhances transcription elongation, potentially through recruitment of co-activators or release of co-repressors with unique roles in elongation. For estrogen-repressed genes, estrogen treatment leads to chromatin structure reconfiguration, thereby disrupting the originally transcription-efficient chromatin structures. Our in silico studies have shown that estrogen regulates gene expression, at least in part, through modifying previously assembled higher-order complexes, rather than by facilitating de novo assembly of machineries. |
| Databáze: | OpenAIRE |
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