ESR1 ChIP-Seq Identifies Distinct Ligand-Free ESR1 Genomic Binding Sites in Human Hepatocytes and Liver Tissue.
ESR1 ChIP-Seq Identifies Distinct Ligand-Free ESR1 Genomic Binding Sites in Human Hepatocytes and Liver Tissue.
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DOI：
10.3390/ijms22031461
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发表时间：
2021-02-02
影响因子：
5.6
通讯作者：
Wang D
中科院分区：
文献类型：
--
作者：
Collins JM;Huo Z;Wang D
雌激素受体α (ESR1)是一种重要的基因转录调节因子，已知可介导雌激素的作用。通常，ESR1被其配体雌激素激活。然而，非配体ESR1在转录调控中的作用一直受到关注。我们最近发现，无配体ESR1是肝脏中几种细胞色素P450 （CYP）基因的关键调节因子，然而，人类肝脏中无配体ESR1尚未在全基因组范围内被表征。为了解决这个问题，ESR1 ChIP-Seq在人类肝脏样本和肝细胞中进行了17 - β -雌二醇（E2）治疗或不治疗。我们在整个基因组中确定了依赖配体和不依赖配体的结合位点。这两种ESR1结合类别表现出不同的基因组定位、途径富集和辅因子共定位，表明ESR1的调节功能取决于配体的可用性。通过分析来自其他人类细胞系的现有ESR1数据，我们发现了一种潜在的与配体无关的ESR1活性，即它与锌指蛋白143 （ZNF143）共富集。此外，我们在包括CYPs在内的许多与药物治疗相关的基因位点附近发现了ESR1结合位点。总的来说，这项研究显示了肝脏中不同的无配体和配体结合的ESR1染色质结合谱，并提示ESR1在药物代谢和药物治疗中的潜在广泛影响。
The estrogen receptor alpha (ESR1) is an important gene transcriptional regulator, known to mediate the effects of estrogen. Canonically, ESR1 is activated by its ligand estrogen. However, the role of unliganded ESR1 in transcriptional regulation has been gaining attention. We have recently shown that ligand-free ESR1 is a key regulator of several cytochrome P450 (CYP) genes in the liver, however ligand-free ESR1 has not been characterized genome-wide in the human liver. To address this, ESR1 ChIP-Seq was conducted in human liver samples and in hepatocytes with or without 17beta-estradiol (E2) treatment. We identified both ligand-dependent and ligand-independent binding sites throughout the genome. These two ESR1 binding categories showed different genomic localization, pathway enrichment, and cofactor colocalization, indicating different ESR1 regulatory function depending on ligand availability. By analyzing existing ESR1 data from additional human cell lines, we uncovered a potential ligand-independent ESR1 activity, namely its co-enrichment with the zinc finger protein 143 (ZNF143). Furthermore, we identified ESR1 binding sites near many gene loci related to drug therapy, including the CYPs. Overall, this study shows distinct ligand-free and ligand-bound ESR1 chromatin binding profiles in the liver and suggests the potential broad influence of ESR1 in drug metabolism and drug therapy.
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DOI：
10.1073/pnas.0903033106
发表时间：
2009-05-05
影响因子：
11.1
作者：
Cardamone, Maria Dafne;Bardella, Chiara;De Bortoli, Michele
通讯作者：
De Bortoli, Michele
影响因子：
16
作者：
Cvoro, A;Tzagarakis-Foster, C;Leitman, DC
通讯作者：
Leitman, DC
转录因子NFIB和YBX1的ERα结合使FGFR2信号传导能够调节乳腺癌中的雌激素反应性。
影响因子：
11.2
作者：
Campbell TM;Castro MAA;de Oliveira KG;Ponder BAJ;Meyer KB
通讯作者：
Meyer KB
影响因子：
16
作者：
Heinz S;Benner C;Spann N;Bertolino E;Lin YC;Laslo P;Cheng JX;Murre C;Singh H;Glass CK
通讯作者：
Glass CK
影响因子：
14.9
作者：
Haeussler M;Zweig AS;Tyner C;Speir ML;Rosenbloom KR;Raney BJ;Lee CM;Lee BT;Hinrichs AS;Gonzalez JN;Gibson D;Diekhans M;Clawson H;Casper J;Barber GP;Haussler D;Kuhn RM;Kent WJ
通讯作者：
Kent WJ