对影响先驱因子约束特性的序列特征的系统解剖揭示了FOXA1和AP-1之间的约束协同作用
Cheng Xu1,2, Holly Kleinschmidt1,2, Jianyu Yang1,2
1Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA.
bioRxiv : the preprint server for biology
|November 21, 2023
概括
像FOXA1这样的先驱转录因子 (PF) 结合特定的DNA序列,受其他因素和局部DNA特征的影响,而不仅仅是染色质状态. 这项研究阐明了PF如何实现具有约束力的选择性.
科学领域:
- 分子生物学分子生物学
- 基因组学就是基因组学.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 先驱转录因子 (PFs) 可以访问封闭的染色质,但只结合少数基因组位点.
- PF结合选择性的机制尚不清楚.
研究的目的:
- 调查控制先驱转录因子 (PF) 结合特异性的序列特征.
- 了解共同结合因子和染色质背景在FOXA1结合中的作用.
主要方法:
- 开发一个高通量测试,ChIP-ISO.
- 整合ChIP-ISO与体外结合试验和神经网络分析.
- 对影响FOXA1结合的序列特征进行系统解剖.
主要成果:
- 联合结合的转录因子AP-1和CEPBPB对FOXA1的结合有显著的影响.
- 在体外,FOXA1和AP-1表现出结合性合作性.
- 局部DNA序列,而不是染色质上下文 (eu-/异染色质),主要决定FOXA1结合.
- AP-1有助于FOXA1.1的细胞类型特定的差异性结合.
结论:
- 已经建立了一个框架来阐明PF约束特异性的遗传规则.
- 局部序列特征和共同结合的TF在调节PF结合中起着至关重要的作用.
- 揭示了先驱转录因子结合的特定环境调节机制.
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