Details

Autor(en) / Beteiligte

• Sérandour, Aurélien A
• Avner, Stéphane
• Oger, Frédérik
• Bizot, Maud
• Percevault, Frédéric
• Lucchetti-Miganeh, Céline
• Palierne, Gaëlle
• Gheeraert, Céline
• Barloy-Hubler, Frédérique
• Péron, Christine Le
• Madigou, Thierry
• Durand, Emmanuelle
• Froguel, Philippe
• Staels, Bart
• Lefebvre, Philippe
• Métivier, Raphaël
• Eeckhoute, Jérôme
• Salbert, Gilles

Titel

Dynamic hydroxymethylation of deoxyribonucleic acid marks differentiation-associated enhancers

Ist Teil von

• Nucleic acids research, 2012-09, Vol.40 (17), p.8255

Ort / Verlag

England

Erscheinungsjahr

2012

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Enhancers are developmentally controlled transcriptional regulatory regions whose activities are modulated through histone modifications or histone variant deposition. In this study, we show by genome-wide mapping that the newly discovered deoxyribonucleic acid (DNA) modification 5-hydroxymethylcytosine (5hmC) is dynamically associated with transcription factor binding to distal regulatory sites during neural differentiation of mouse P19 cells and during adipocyte differentiation of mouse 3T3-L1 cells. Functional annotation reveals that regions gaining 5hmC are associated with genes expressed either in neural tissues when P19 cells undergo neural differentiation or in adipose tissue when 3T3-L1 cells undergo adipocyte differentiation. Furthermore, distal regions gaining 5hmC together with H3K4me2 and H3K27ac in P19 cells behave as differentiation-dependent transcriptional enhancers. Identified regions are enriched in motifs for transcription factors regulating specific cell fates such as Meis1 in P19 cells and PPARγ in 3T3-L1 cells. Accordingly, a fraction of hydroxymethylated Meis1 sites were associated with a dynamic engagement of the 5-methylcytosine hydroxylase Tet1. In addition, kinetic studies of cytosine hydroxymethylation of selected enhancers indicated that DNA hydroxymethylation is an early event of enhancer activation. Hence, acquisition of 5hmC in cell-specific distal regulatory regions may represent a major event of enhancer progression toward an active state and participate in selective activation of tissue-specific genes.