单核转录因子的co-TF依赖的分歧涉及多个内在无序的区域,影响激活和自身抑制
Lindsey F Snyder1, Emily M O'Brien2, Jia Zhao2
1Interdisciplinary Graduate Program in Genetics, University of Iowa, Iowa City, IA.
bioRxiv : the preprint server for biology
|September 10, 2024
概括
由内在无序区域 (IDR) 驱动的转录因子 (TF) 共同依赖的进化,重塑基因调节网络. 这项研究揭示了TF相互依赖如何演变,影响酵母菌中的基因调节特异性和信息整合.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 进化生物学 进化生物学
背景情况:
- 通过多个转录因子 (TF) 进行组合控制对于真核生物的基因调节至关重要,增强了特异性和信息整合.
- 对于TF相互依赖的机制和进化基础的理解仍然很差.
- 酵母中的酸盐饥饿 (PHO) 反应为研究TF共同依赖的自然变异提供了一个模型.
研究的目的:
- 研究共转录因子 (co-TF) 依赖的分子机制和进化驱动因素.
- 了解共同TF依赖的变化如何导致基因调节网络的重新连接.
- 为了比较*Saccharomyces cerevisiae*和*Candida glabrata*之间的PHO反应中的co-TF依赖性.
主要方法:
- 在酵母菌种 (*Saccharomyces cerevisiae*和 *Candida glabrata*) 中对TF依赖的比较分析.
- 生物化学测试以确定DNA结合亲和力.
- 机器学习预测和酵母单混合测试以确定功能区域.
- 对内在无序区域 (IDR) 的分析及其对TF活动的影响.
主要成果:
- 与*Saccharomyces cerevisiae* Pho4 (ScPho4) 相比, *Candida glabrata* Pho4 (CgPho4) 对其共同TF Pho2的依赖性降低,并调节了较大的基因组.
- CgPho4以更高的亲和力结合DNA,其活性由两种增强主激活域的IDRs增强.
- 在ScPho4中的IDR就像一把双刃剑,在没有Pho2的情况下调节自身抑制,在Pho2的情况下增强活性.
结论:
- IDRs的进化分歧是改变co-TF依赖性的关键驱动因素.
- 改变的co-TF依赖,由IDR进化介导,可以显著重塑基因调节网络.
- 这项研究为基因调节和TF相互依赖的演变提供了分子洞察力.
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