Cytosine modifications modulate the chromatin architecture of transcriptional enhancers.

Abstract:

:Epigenetic mechanisms are believed to play key roles in the establishment of cell-specific transcription programs. Accordingly, the modified bases 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) have been observed in DNA of genomic regulatory regions such as enhancers, and oxidation of 5mC into 5hmC by Ten-eleven translocation (TET) proteins correlates with enhancer activation. However, the functional relationship between cytosine modifications and the chromatin architecture of enhancers remains elusive. To gain insights into their function, 5mC and 5hmC levels were perturbed by inhibiting DNA methyltransferases and TETs during differentiation of mouse embryonal carcinoma cells into neural progenitors, and chromatin characteristics of enhancers bound by the pioneer transcription factors FOXA1, MEIS1, and PBX1 were interrogated. In a large fraction of the tested enhancers, inhibition of DNA methylation was associated with a significant increase in monomethylation of H3K4, a characteristic mark of enhancer priming. In addition, at some specific enhancers, 5mC oxidation by TETs facilitated chromatin opening, a process that may stabilize MEIS1 binding to these genomic regions.

journal_name

Genome Res

journal_title

Genome research

authors

Mahé EA,Madigou T,Sérandour AA,Bizot M,Avner S,Chalmel F,Palierne G,Métivier R,Salbert G

doi

10.1101/gr.211466.116

subject

Has Abstract

pub_date

2017-06-01 00:00:00

pages

947-958

issue

6

eissn

1088-9051

issn

1549-5469

pii

gr.211466.116

journal_volume

27

pub_type

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