DNA Demethylation Dynamics in the Human Prenatal Germline

Sofia Gkountela; Kelvin X Zhang; Tiasha A Shafiq; Wen-Wei Liao; Joseph Hargan-Calvopiña; Pao-Yang Chen; Amander T Clark

doi:10.1016/j.cell.2015.05.012

DNA Demethylation Dynamics in the Human Prenatal Germline

Cell. 2015 Jun 4;161(6):1425-36. doi: 10.1016/j.cell.2015.05.012. Epub 2015 May 21.

Authors

Sofia Gkountela¹, Kelvin X Zhang², Tiasha A Shafiq¹, Wen-Wei Liao³, Joseph Hargan-Calvopiña¹, Pao-Yang Chen⁴, Amander T Clark⁵

Affiliations

¹ Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
² Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
³ Institute of Plant and Microbial Biology, Academia Sinica, Taipei 11529, Taiwan.
⁴ Institute of Plant and Microbial Biology, Academia Sinica, Taipei 11529, Taiwan. Electronic address: paoyang@gate.sinica.edu.tw.
⁵ Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: clarka@ucla.edu.

Abstract

Global DNA demethylation in humans is a fundamental process that occurs in pre-implantation embryos and reversion to naive ground state pluripotent stem cells (PSCs). However, the extent of DNA methylation reprogramming in human germline cells is unknown. Here, we performed whole-genome bisulfite sequencing (WGBS) and RNA-sequencing (RNA-seq) of human prenatal germline cells from 53 to 137 days of development. We discovered that the transcriptome and methylome of human germline is distinct from both human PSCs and the inner cell mass (ICM) of human blastocysts. Using this resource to monitor the outcome of global DNA demethylation with reversion of primed PSCs to the naive ground state, we uncovered hotspots of ultralow methylation at transposons that are protected from demethylation in the germline and ICM. Taken together, the human germline serves as a valuable in vivo tool for monitoring the epigenome of cells that have emerged from a global DNA demethylation event.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Blastocyst / metabolism*
Blastocyst Inner Cell Mass
DNA Methylation*
Embryo, Mammalian / metabolism*
Embryonic Stem Cells / metabolism
Female
Gene Expression Profiling
Germ Cells / metabolism*
Humans
Male

Associated data

GEO/GSE63392
GEO/GSE63393

Abstract

Publication types

MeSH terms

Associated data

Grants and funding