Unknown

Dataset Information

0

Dynamic hydroxymethylation of deoxyribonucleic acid marks differentiation-associated enhancers.


ABSTRACT: 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 PPAR? 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.

SUBMITTER: Serandour AA 

PROVIDER: S-EPMC3458548 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

altmetric image

Publications


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  ...[more]

Similar Datasets

2012-06-03 | E-GEOD-27436 | biostudies-arrayexpress
2012-06-04 | GSE27436 | GEO
| S-EPMC8703110 | biostudies-literature
| S-EPMC9531456 | biostudies-literature
| S-EPMC4515125 | biostudies-literature
| S-EPMC7611323 | biostudies-literature
| S-EPMC4176165 | biostudies-literature
| S-EPMC7607866 | biostudies-literature
| S-EPMC4154669 | biostudies-literature
| S-EPMC5888657 | biostudies-literature