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Decoding the dynamic DNA methylation and hydroxymethylation landscapes in endodermal lineage intermediates during pancreatic differentiation of hESC
Li, Jia1; Wu, Xinwei2; Zhou, Yubin3,4; Lee, Minjung1; Guo, Lei1; Han, Wei1; Mo, William1; Cao, Wen-ming5; Sun, Deqiang1,6; Xie, Ruiyu2; Huang, Yun1,6
2018-04-06
Source PublicationNUCLEIC ACIDS RESEARCH
ISSN0305-1048
Volume46Issue:6Pages:2883-2900
Abstract

Dynamic changes in DNA methylation and demethylation reprogram transcriptional outputs to instruct lineage specification during development. Here, we applied an integrative epigenomic approach to unveil DNA (hydroxy) methylation dynamics representing major endodermal lineage intermediates during pancreatic differentiation of human embryonic stem cells (hESCs). We found that 5-hydroxymethylcytosine (5hmC) marks genomic regions to be demethylated in the descendent lineage, thus reshaping the DNA methylation landscapes during pancreatic lineage progression. DNA hydroxymethylation is positively correlated with enhancer activities and chromatin accessibility, as well as the selective binding of lineage-specific pioneer transcription factors, during pancreatic differentiation. We further discovered enrichment of hydroxymethylated regions (termed '5hmC-rim') at the boundaries of large hypomethylated functional genomic regions, including super-enhancer, DNA methylation canyon and broad-H3K4me3 peaks. We speculate that '5hmC-rim' might safeguard low levels of cytosine methylation at these regions. Our comprehensive analysis highlights the importance of dynamic changes of epigenetic landscapes in driving pancreatic differentiation of hESC.

DOI10.1093/nar/gky063
URLView the original
Indexed BySCI
Language英语
WOS Research AreaBiochemistry & Molecular Biology
WOS SubjectBiochemistry & Molecular Biology
WOS IDWOS:000429009500019
PublisherOXFORD UNIV PRESS
The Source to ArticleWOS
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Cited Times [WOS]:15   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Affiliation1.Center for Epigenetics & Disease Prevention, Institute of Biosciences and Technology, College of Medicine, Texas A&M University, Houston, TX 77030, USA
2.Faculty of Health of Sciences, University of Macau, Macau 999078, China
3.Center for Translational Cancer Research, Institute of Biosciences and Technology, College of Medicine, Texas A&M University, Houston, TX 77030, USA
4.Department of Medical Physiology, College of Medicine, Texas A&M University, Temple, TX 76504, USA
5.Department of Breast Medical Oncology, Zhejiang Cancer Hospital, Hangzhou 310022, China
6.Department of Molecular & Cellular Medicine, College of Medicine, Texas A&M University, College Station, TX 77843, USA
Recommended Citation
GB/T 7714
Li, Jia,Wu, Xinwei,Zhou, Yubin,et al. Decoding the dynamic DNA methylation and hydroxymethylation landscapes in endodermal lineage intermediates during pancreatic differentiation of hESC[J]. NUCLEIC ACIDS RESEARCH,2018,46(6):2883-2900.
APA Li, Jia.,Wu, Xinwei.,Zhou, Yubin.,Lee, Minjung.,Guo, Lei.,...&Huang, Yun.(2018).Decoding the dynamic DNA methylation and hydroxymethylation landscapes in endodermal lineage intermediates during pancreatic differentiation of hESC.NUCLEIC ACIDS RESEARCH,46(6),2883-2900.
MLA Li, Jia,et al."Decoding the dynamic DNA methylation and hydroxymethylation landscapes in endodermal lineage intermediates during pancreatic differentiation of hESC".NUCLEIC ACIDS RESEARCH 46.6(2018):2883-2900.
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