The Pioneer Transcription Factor FoxA Maintains an Accessible Nucleosome Configuration at Enhancers for Tissue-Specific Gene Activation
| Autor: | Klaus H. Kaestner, Greg Donahue, Dolim Lee, Akshay Kakumanu, Jason A. Watts, Shaun Mahony, B. Franklin Pugh, Kenneth S. Zaret, Makiko Iwafuchi-Doi |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Hepatocyte Nuclear Factor 3-alpha Transcription Genetic Enhancer RNAs Article Histones 03 medical and health sciences Mice Histone methylation Animals Enhancer Promoter Regions Genetic Molecular Biology Transcription factor Genetics biology Pioneer factor Eukaryotic transcription Promoter Cell Biology Cell biology Nucleosomes 030104 developmental biology Histone Enhancer Elements Genetic Liver Organ Specificity biology.protein Hepatocyte Nuclear Factor 3-beta Hepatocyte Nuclear Factor 3-gamma |
| Zdroj: | Molecular cell. 62(1) |
| ISSN: | 1097-4164 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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