• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

人支持细胞中组蛋白乙酰转移酶P300对OX9基因的表观遗传调控。

Epigenetic control of OX9 gene by the histone acetyltransferase P300 in human Sertoli cells.

作者信息

González Daniel, Peña María José, Bernal Camila, García-Acero Mary, Manotas Maria Carolina, Suarez-Obando Fernando, Rojas Adriana

机构信息

Institute of Human Genetics, Faculty of Medicine, Pontificia Universidad Javeriana. Carrera 7 No. 40-62, 110231, Bogotá, Colombia.

Department of Genetics, University of Córdoba, 14071, Córdoba, Spain.

出版信息

Heliyon. 2024 Jun 18;10(12):e33173. doi: 10.1016/j.heliyon.2024.e33173. eCollection 2024 Jun 30.

DOI:10.1016/j.heliyon.2024.e33173
PMID:39022079
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11252772/
Abstract

BACKGROUND

The transcription factor SOX9 is a key regulator of male sexual development and Sertoli cell differentiation. Altered OX9 expression has been implicated in the pathogenesis of disorders of sexual development (DSD) in mammals. However, limited information exists regarding the epigenetic mechanisms governing its transcriptional control during sexual development.

METHODS

This study employed real-time PCR (qPCR), immunofluorescence (IIF), and chromatin immunoprecipitation (ChIP) assays to investigate the epigenetic mechanisms associated with OX9 gene transcriptional control in human and mouse Sertoli cell lines. To identify the specific epigenetic enzymes involved in SOX9 epigenetic control, functional assays using siRNAs for P300, GCN5, and WDR5 were performed.

RESULTS

The transcriptional activation of SOX9 was associated with selective deposition of active histone modifications, such as H3K4me3 and H3K27ac, at its enhancer and promoter regions. Importantly, the histone acetyltransferase P300 was found to be significantly enriched at the SOX9 enhancers, co-localizing with the H3K27ac and the SOX9 transcription factor. Silencing of P300 led to decreased SOX9 expression and reduced H3K27ac levels at the eSR-A and e-ALDI enhancers, demonstrating the crucial role of P300-mediated histone acetylation in SOX9 transcriptional activation. Interestingly, another histone lysine acetyltransferases like GNC5 and methyltransferases as the Trithorax/COMPASS-like may also have a relevant role in male sexual differentiation.

CONCLUSIONS

Histone acetylation by P300 at SOX9 enhancers, is a key mechanism governing the transcriptional control of this essential regulator of male sexual development. These findings provide important insights into the epigenetic basis of sexual differentiation and the potential pathogenesis of DSDs.

摘要

背景

转录因子SOX9是男性性发育和支持细胞分化的关键调节因子。OX9表达的改变与哺乳动物性发育障碍（DSD）的发病机制有关。然而，关于性发育过程中其转录调控的表观遗传机制的信息有限。

方法

本研究采用实时定量PCR（qPCR）、免疫荧光（IIF）和染色质免疫沉淀（ChIP）分析，以研究人类和小鼠支持细胞系中与OX9基因转录调控相关的表观遗传机制。为了确定参与SOX9表观遗传调控的特定表观遗传酶，使用针对P300、GCN5和WDR5的小干扰RNA（siRNA）进行了功能分析。

结果

SOX9的转录激活与其增强子和启动子区域活性组蛋白修饰（如H3K4me3和H3K27ac）的选择性沉积有关。重要的是，发现组蛋白乙酰转移酶P300在SOX9增强子处显著富集，与H3K27ac和SOX9转录因子共定位。P300的沉默导致SOX9表达降低以及eSR-A和e-ALDI增强子处H3K27ac水平降低，表明P300介导的组蛋白乙酰化在SOX9转录激活中起关键作用。有趣的是，其他组蛋白赖氨酸乙酰转移酶如GNC5和甲基转移酶（如类三体胸苷/COMPASS样）在男性性分化中可能也起相关作用。

结论

P300在SOX9增强子处的组蛋白乙酰化是控制男性性发育这一关键调节因子转录调控的关键机制。这些发现为性分化的表观遗传基础以及DSD的潜在发病机制提供了重要见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f30/11252772/f4c6a655265a/mmcfigs8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f30/11252772/da41e3fae68a/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f30/11252772/0ed42e15a633/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f30/11252772/59d145e75567/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f30/11252772/1001257ebbab/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f30/11252772/18877662b297/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f30/11252772/cdfcece4894d/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f30/11252772/eb151fa245db/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f30/11252772/5dbe6b5885e4/mmcfigs1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f30/11252772/a4a83576089e/mmcfigs2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f30/11252772/485d9139b851/mmcfigs3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f30/11252772/afdcff508635/mmcfigs4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f30/11252772/aafa70694db8/mmcfigs5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f30/11252772/c30dede46745/mmcfigs6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f30/11252772/091434494370/mmcfigs7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f30/11252772/f4c6a655265a/mmcfigs8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f30/11252772/da41e3fae68a/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f30/11252772/0ed42e15a633/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f30/11252772/59d145e75567/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f30/11252772/1001257ebbab/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f30/11252772/18877662b297/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f30/11252772/cdfcece4894d/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f30/11252772/eb151fa245db/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f30/11252772/5dbe6b5885e4/mmcfigs1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f30/11252772/a4a83576089e/mmcfigs2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f30/11252772/485d9139b851/mmcfigs3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f30/11252772/afdcff508635/mmcfigs4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f30/11252772/aafa70694db8/mmcfigs5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f30/11252772/c30dede46745/mmcfigs6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f30/11252772/091434494370/mmcfigs7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f30/11252772/f4c6a655265a/mmcfigs8.jpg

相似文献

1
Epigenetic control of OX9 gene by the histone acetyltransferase P300 in human Sertoli cells.人支持细胞中组蛋白乙酰转移酶P300对OX9基因的表观遗传调控。
Heliyon. 2024 Jun 18;10(12):e33173. doi: 10.1016/j.heliyon.2024.e33173. eCollection 2024 Jun 30.
2
Loci-specific histone acetylation profiles associated with transcriptional coactivator p300 during early myoblast differentiation.与早期成肌细胞分化过程中的转录共激活因子 p300 相关的特异性组蛋白乙酰化图谱。
Epigenetics. 2018;13(6):642-654. doi: 10.1080/15592294.2018.1489659. Epub 2018 Jul 30.
3
A UTX-MLL4-p300 Transcriptional Regulatory Network Coordinately Shapes Active Enhancer Landscapes for Eliciting Transcription.一个UTX-MLL4-p300转录调控网络协同塑造活性增强子景观以引发转录。
Mol Cell. 2017 Jul 20;67(2):308-321.e6. doi: 10.1016/j.molcel.2017.06.028.
4
The pioneer factor activity of c-Myb involves recruitment of p300 and induction of histone acetylation followed by acetylation-induced chromatin dissociation.c-Myb 的先驱因子活性涉及募集 p300 和诱导组蛋白乙酰化，随后是乙酰化诱导的染色质解离。
Epigenetics Chromatin. 2018 Jun 28;11(1):35. doi: 10.1186/s13072-018-0208-y.
5
Sox9 and p300 cooperatively regulate chromatin-mediated transcription.Sox9和p300协同调节染色质介导的转录。
J Biol Chem. 2005 Oct 21;280(42):35203-8. doi: 10.1074/jbc.M502409200. Epub 2005 Aug 18.
6
Histone Acetyltransferase-Dependent Pathways Mediate Upregulation of NADPH Oxidase 5 in Human Macrophages under Inflammatory Conditions: A Potential Mechanism of Reactive Oxygen Species Overproduction in Atherosclerosis.组蛋白乙酰转移酶依赖的途径介导炎症条件下人巨噬细胞中 NADPH 氧化酶 5 的上调：动脉粥样硬化中活性氧过度产生的潜在机制。
Oxid Med Cell Longev. 2019 Sep 2;2019:3201062. doi: 10.1155/2019/3201062. eCollection 2019.
7
A dynamic H3K27ac signature identifies VEGFA-stimulated endothelial enhancers and requires EP300 activity.一个动态的 H3K27ac 特征可以识别 VEGFA 刺激的血管内皮增强子，并需要 EP300 活性。
Genome Res. 2013 Jun;23(6):917-27. doi: 10.1101/gr.149674.112. Epub 2013 Apr 1.
8
DBC1 is a key positive regulator of enhancer epigenomic writers KMT2D and p300.DBC1 是增强子表观遗传 writers KMT2D 和 p300 的关键正调控因子。
Nucleic Acids Res. 2022 Aug 12;50(14):7873-7888. doi: 10.1093/nar/gkac585.
9
Sodium arsenite exposure inhibits histone acetyltransferase p300 for attenuating H3K27ac at enhancers in mouse embryonic fibroblast cells.亚砷酸钠暴露抑制组蛋白乙酰转移酶 p300，减弱了增强子处 H3K27ac 在小鼠胚胎成纤维细胞中的水平。
Toxicol Appl Pharmacol. 2018 Oct 15;357:70-79. doi: 10.1016/j.taap.2018.08.011. Epub 2018 Aug 18.
10
Pax6 associates with H3K4-specific histone methyltransferases Mll1, Mll2, and Set1a and regulates H3K4 methylation at promoters and enhancers.Pax6与H3K4特异性组蛋白甲基转移酶Mll1、Mll2和Set1a相关联，并调节启动子和增强子处的H3K4甲基化。
Epigenetics Chromatin. 2016 Sep 9;9(1):37. doi: 10.1186/s13072-016-0087-z. eCollection 2016.

引用本文的文献

1
Unmasking the Epigenome: Insights into Testicular Cell Dynamics and Reproductive Function.揭示表观基因组：对睾丸细胞动态和生殖功能的见解
Int J Mol Sci. 2025 Jul 28;26(15):7305. doi: 10.3390/ijms26157305.

本文引用的文献

1
The genetic diagnosis of rare endocrine disorders of sex development and maturation: a survey among Endo-ERN centres.罕见性发育和成熟内分泌疾病的基因诊断：一项针对内分泌罕见病欧洲参考网络（Endo-ERN）中心的调查。
Endocr Connect. 2022 Nov 14;11(12). doi: 10.1530/EC-22-0367. Print 2022 Dec 1.
2
SOX Genes and Their Role in Disorders of Sex Development.SOX 基因及其在性别发育障碍中的作用。
Sex Dev. 2022;16(2-3):80-91. doi: 10.1159/000524453. Epub 2022 Jun 27.
3
A synthetic lethality screen reveals ING5 as a genetic dependency of catalytically dead Set1A/COMPASS in mouse embryonic stem cells.
一项合成致死性筛选揭示了 ING5 是小鼠胚胎干细胞中催化失活的 Set1A/COMPASS 的遗传依赖性。
Proc Natl Acad Sci U S A. 2022 May 10;119(19):e2118385119. doi: 10.1073/pnas.2118385119. Epub 2022 May 2.
4
Enhancers are activated by p300/CBP activity-dependent PIC assembly, RNAPII recruitment, and pause release.增强子通过 p300/CBP 活性依赖性 PIC 组装、RNAPII 募集和暂停释放来激活。
Mol Cell. 2021 May 20;81(10):2166-2182.e6. doi: 10.1016/j.molcel.2021.03.008. Epub 2021 Mar 24.
5
An atlas of the protein-coding genes in the human, pig, and mouse brain.人类、猪和鼠脑的蛋白质编码基因图谱。
Science. 2020 Mar 6;367(6482). doi: 10.1126/science.aay5947.
6
Disorders of Sexual Development: Current Status and Progress in the Diagnostic Approach.性发育障碍：诊断方法的现状与进展
Curr Urol. 2020 Jan;13(4):169-178. doi: 10.1159/000499274. Epub 2020 Jan 7.
7
Robust statistical methods in R using the WRS2 package.使用 WRS2 包在 R 中进行稳健的统计方法。
Behav Res Methods. 2020 Apr;52(2):464-488. doi: 10.3758/s13428-019-01246-w.
8
The regulation of Sox9 expression in the gonad.Sox9 表达在性腺中的调控。
Curr Top Dev Biol. 2019;134:223-252. doi: 10.1016/bs.ctdb.2019.01.004. Epub 2019 Feb 13.
9
Human sex reversal is caused by duplication or deletion of core enhancers upstream of SOX9.人类性别反转是由 SOX9 上游核心增强子的重复或缺失引起的。
Nat Commun. 2018 Dec 14;9(1):5319. doi: 10.1038/s41467-018-07784-9.
10
Sex reversal following deletion of a single distal enhancer of .单个. 的远端增强子缺失导致的性别反转
Science. 2018 Jun 29;360(6396):1469-1473. doi: 10.1126/science.aas9408. Epub 2018 Jun 14.