意想不到的核激素受体和染色质动态调节雌激周期依赖的基因表达
Wendy N Jefferson1, Tianyuan Wang2, Elizabeth Padilla-Banks1
1Reproductive & Developmental Biology Laboratory, Research Triangle Park, NC 27709, USA.
雌激素受体α (ERα) 和孕激素受体 (PGR) 在小鼠子宫发育过程中共同结合,不像预期的那样交替. 低氧诱导因子2A (HIF2A) 在雌性期独立调节基因表达.
科学领域:
- 生殖生物学 生殖生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 基因组学就是基因组学.
背景情况:
- 激素介导的染色质变化控制基因表达.
- 雌激素和孕激素对子宫基因表达的生理调节仍然不清楚.
研究的目的:
- 在小鼠雌激循环期间调查激素受体占用率,染色质可访问性和结构的体内动态.
- 阐明由雌激素和孕激素对子宫基因表达调节的机制.
主要方法:
- 组合的RNA-seq,ATAC-seq,HiC-seq和ChIP-seq. 这些组合的RNA-seq,ATAC-seq,HiC-seq和ChIP-seq.
- 分析了小鼠在期 (高雌激素) 和期 (高孕激素) 的子宫.
- 进行了动机分析和条件基因删除研究.
主要成果:
- 雌激素受体α (ERα) 和孕激素受体 (PGR) 在diestrus期间出乎意料地相互结合,并在estrus期间丢失.
- 低氧诱导因子2A (HIF2A) 在调节基因表达方面发挥着新的作用,独立于ERα或PGR.
- 在期期间,ERα复合体包括PGR和cohesin.
- HiC-seq揭示了染色体结构的变化,包括增强器切换,与受体结合和HIF2A活性协调.
结论:
- 整个雌激周期的子宫基因表达受到雌激期的动态ERα和PGR联合结合以及雌激期的非激素转录因子 (如HIF2A) 的调节.
- 复杂的染色体结构改造对于循环基因表达至关重要.
- 揭示了HIF2A在女性生殖道中的新型调节作用.
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