Mol Cell:挑战常规!核小体也存在于活性增强子位点上
来源:生物谷 2016-04-12 17:50
一项新的研究对DNA上的调控序列的结构如何在细胞中组装提供新的认识。
2016年4月12日/生物谷BIOON/--在一项新的研究中,来自美国宾夕法尼亚大学佩雷尔曼医学院的研究人员对DNA上的调控序列的结构如何在细胞中组装提供新的认识。相关研究结果发表在2016年4月7日那期Molecular Cell期刊上,论文标题为“The Pioneer Transcription Factor FoxA Maintains an Accessible Nucleosome Configuration at Enhancers for Tissue-Specific Gene Activation”。论文通信作者、佩雷尔曼医学院再生医学研究所主任、细胞与发育生物学教授Ken Zaret博士说,“这项研究对被称作增强子的基因序列在调控基因活性上所发挥的作用提供更好的理解。”
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The Pioneer Transcription Factor FoxA Maintains an Accessible Nucleosome Configuration at Enhancers for Tissue-Specific Gene Activation
doi:10.1016/j.molcel.2016.03.001
Makiko Iwafuchi-Doi, Greg Donahue, Akshay Kakumanu, Jason A. Watts, Shaun Mahony, B. Franklin Pugh, Dolim Lee, Klaus H. Kaestner, Kenneth S. Zaret
Nuclear DNA wraps around core histones to form nucleosomes, which restricts the binding of transcription factors to gene regulatory sequences. Pioneer transcription factors can bind DNA sites on nucleosomes and initiate gene regulatory events, often leading to the local opening of chromatin. However, the nucleosomal configuration of open chromatin and the basis for its regulation is unclear. We combined low and high levels of micrococcal nuclease (MNase) digestion along with core histone mapping to assess the nucleosomal configuration at enhancers and promoters in mouse liver. We find that MNase-accessible nucleosomes, bound by transcription factors, are retained more at liver-specific enhancers than at promoters and ubiquitous enhancers. The pioneer factor FoxA displaces linker histone H1, thereby keeping enhancer nucleosomes accessible in chromatin and allowing other liver-specific transcription factors to bind and stimulate transcription. Thus, nucleosomes are not exclusively repressive to gene regulation when they are retained with, and exposed by, pioneer factors.
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