期刊
NATURE CHEMISTRY
卷 10, 期 12, 页码 1258-1266出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41557-018-0149-x
关键词
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资金
- Wellcome Trust [099232/z/12/z, 095645/Z/11/Z]
- Cancer Research UK [C14303/A17197]
- A*STAR (Singapore)
- Leukaemia Foundation Australia
- Howard Hughes Medical Institute
- BBSRC [BB/K010867/1]
- BBSRC [BBS/E/B/000C0421, BBS/E/B/0000H334] Funding Source: UKRI
Nucleosomes are the basic unit of chromatin that help the packaging of genetic material while controlling access to the genetic information. The underlying DNA sequence, together with transcription-associated proteins and chromatin remodelling complexes, are important factors that influence the organization of nucleosomes. Here, we show that the naturally occurring DNA modification, 5-formylcytosine (5fC) is linked to tissue-specific nucleosome organization. Our study reveals that 5fC is associated with increased nucleosome occupancy in vitro and in vivo. We demonstrate that 5fC-associated nucleosomes at enhancers in the mammalian hindbrain and heart are linked to elevated gene expression. Our study also reveals the formation of a reversible-covalent Schiff base linkage between lysines of histone proteins and 5fC within nucleosomes in a cellular environment. We define their specific genomic loci in mouse embryonic stem cells and look into the biological consequences of these DNA-histone Schiff base sites. Collectively, our findings show that 5fC is a determinant of nucleosome organization and plays a role in establishing distinct regulatory regions that control transcription.
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