RT Journal Article
SR Electronic
T1 Spatiotemporal DNA Methylome Dynamics of the Developing Mammalian Fetus
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 166744
DO 10.1101/166744
A1 Yupeng He
A1 Manoj Hariharan
A1 David U. Gorkin
A1 Diane E. Dickel
A1 Chongyuan Luo
A1 Rosa G. Castanon
A1 Joseph R. Nery
A1 Ah Young Lee
A1 Brian A. Williams
A1 Diane Trout
A1 Henry Amrhein
A1 Rongxin Fang
A1 Huaming Chen
A1 Bin Li
A1 Axel Visel
A1 Len A. Pennacchio
A1 Bing Ren
A1 Joseph R. Ecker
YR 2017
UL http://biorxiv.org/content/early/2017/07/21/166744.abstract
AB Genetic studies have revealed an essential role for cytosine DNA methylation in mammalian development. However, its spatiotemporal distribution in the developing embryo remains obscure. Here, we profiled the methylome landscapes of 12 mouse tissues/organs at 8 developmental stages spanning from early embryogenesis to birth. Indepth analysis of these spatiotemporal epigenome maps systematically delineated ~2 million methylation variant regions and uncovered widespread methylation dynamics at nearly one-half million tissue-specific enhancers, whose human counterparts were enriched for variants involved in genetic diseases. Strikingly, these predicted regulatory elements predominantly lose CG methylation during fetal development, whereas the trend is reversed after birth. Accumulation of non-CG methylation within gene bodies of key developmental transcription factors coincided with their transcriptional repression during later stages of fetal development. These spatiotemporal epigenomic maps provide a valuable resource for studying gene regulation during mammalian tissue/organ progression and for pinpointing regulatory elements involved in human developmental diseases.