乙酰化组蛋白肽的细胞内递送会抑制天然溴结构域与染色质的相互作用，并损害有丝分裂进程。
Intracellular delivery of acetyl-histone peptides inhibits native bromodomain-chromatin interactions and impairs mitotic progression.
作者信息
Nishiyama Akira, Mochizuki Kazuki, Mueller Florian, Karpova Tatiana, McNally James G, Ozato Keiko
机构信息
Laboratory of Molecular Growth Regulation, Genomics and Differentiation Program, National Institutes of Child Health and Human Development, National Institutes of Health, Building 6, Room 2A01, 6 Center Drive, Bethesda, MD 20892-2753, United States.
出版信息
FEBS Lett. 2008 Apr 30;582(10):1501-7. doi: 10.1016/j.febslet.2008.03.044. Epub 2008 Apr 7.
Abstract
Bromodomains present in Brd4 and other chromatin proteins interact with acetylated histones to regulate transcription and cell growth. To study Brd4-chromatin interactions in vivo, histone H4 tail peptides were fused to a synthetic protein transduction domain (PTD) derived from the human immunodeficiency virus Tat and delivered into cultured cells. Acetyl-H4 peptides, but not unacetylated H4 peptides inhibited real time Brd4-chromatin interactions in living cells as assessed by fluorescence recovery after photobleaching assays. The acetyl-H4 peptides also inhibited an interaction of Brd4 with chromosomes during mitosis and reduced cell growth potential. Together, PTD-based delivery of histone tail peptides offers a novel means to study the mechanism and biological significance of bromodomain-chromatin interactions in vivo.
摘要
Brd4及其他染色质蛋白中的溴结构域与乙酰化组蛋白相互作用，以调节转录和细胞生长。为了在体内研究Brd4与染色质的相互作用，将组蛋白H4尾肽与源自人类免疫缺陷病毒Tat的合成蛋白转导结构域（PTD）融合，并导入培养细胞中。通过光漂白后荧光恢复分析评估，乙酰化H4肽而非未乙酰化的H4肽抑制了活细胞中实时Brd4与染色质的相互作用。乙酰化H4肽还抑制了有丝分裂期间Brd4与染色体的相互作用，并降低了细胞生长潜力。总之，基于PTD的组蛋白尾肽递送为研究体内溴结构域与染色质相互作用的机制及生物学意义提供了一种新方法。
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