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通过协调p300乙转移酶和FACT复合体,RSF1调节p53的转录活动

Yungyeong Heo¹, Yonghyeon Kim¹, Won Chung Lim²

¹Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, Suwon, Republic of Korea; Department of Biomedical Sciences, The Graduate School, Ajou University, Suwon, 443-721, Republic of Korea.

Biochemical and biophysical research communications

|November 23, 2024

概括

重塑和间隔因子1 (RSF1) 在DNA损伤后对p53依赖基因转录至关重要. RSF1促进p53乙化和招募DNA修复和细胞存活的关键蛋白质.

科学领域:

分子生物学分子生物学
细胞生物学细胞生物学
遗传学遗传学是一个

背景情况:

在DNA受损后,p53依赖基因转录对DNA修复和细胞存活至关重要.
改造和间隔因子1 (RSF1) 之前已被确定为对p53依赖基因转录至关重要的.
通过RSF1影响p53活动的精确机制尚未完全阐明.

研究的目的:

调查RSF1在调节p53转录活性中的作用,以应对DNA损伤.
确定RSF1枯竭如何影响p53乙化和转录机械的招募.
阐明RSF1促进p53-依赖基因表达的分子机制.

主要方法:

使用淘汰模式来消耗RSF1.
西部涂抹以评估p53乙化水平 (乙化-lys382).
同免疫沉检测RSF1和p300乙转移酶之间的相互作用.
染色体免疫沉 (ChIP) 试验分析了CDKN1A基因p300,TBP和FACT复合体子单元 (SSRP1,SPT16) 的占用情况.
在CDKN1A基因位点对基因子修饰 (H3K27ac,H3K4me1) 的分析.

主要成果:

减少RSF1显著降低了p53在Lys382的乙化水平,这是其转录活性的关键调节者.
发现RSF1在以太化物诱导的DNA损伤后与p300乙转移酶共同沉.
染色体免疫沉试验显示,RSF1淘汰细胞中的CDKN1A基因增强器区域p300和TBP的积累减少.
此外,RSF1的枯竭还导致FACT复杂子单元 (SSRP1,SPT16) 与CDKN1A基因的促进体的结合减少.
与这些变化相关,在CDKN1A位点,活性增强剂和促进剂 (H3K27ac,H3K4me1) 的基因组标记减少了.

结论:

在DNA受损后,RSF1在促进p21 (编码由CDKN1A) 等p53依赖基因的转录中发挥着关键作用.
通过增强p53乙化,RSF1促进了p53的转录活性.
RSF1促进p300乙转移酶向增强剂和FACT复合体向CDKN1A基因的促进剂的招募,从而促进转录.

关键词:

在DNA损伤和修复过程中.改造和间隔因素1 改造和间隔因素1 染色质的动态染色质的动态在p2121中,在 p53 里,p53 是一个 p53 号码.

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