RT Journal
A1 Mahé, Elise A.
A1 Madigou, Thierry
A1 Sérandour, Aurélien A.
A1 Bizot, Maud
A1 Avner, Stéphane
A1 Chalmel, Frédéric
A1 Palierne, Gaëlle
A1 Métivier, Raphaël
A1 Salbert, Gilles
T1 Cytosine modifications modulate the chromatin architecture of transcriptional enhancers
JF Genome Research 
JO Genome Research 
YR 2017 
FD June 01 
VO 27 
IS 6 
SP 947 
OP 958 
DO 10.1101/gr.211466.116 
UL http://genome.cshlp.org/content/27/6/947.abstract 
AB 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.