title: DNA Demethylation Dynamics in the Human Prenatal Germline.
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.
authors.affiliation: Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Sofia
authors.initials: S
authors.lastname: Gkountela
authors.affiliation: Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Kelvin X
authors.initials: KX
authors.lastname: Zhang
authors.affiliation: Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Tiasha A
authors.initials: TA
authors.lastname: Shafiq
authors.affiliation: Institute of Plant and Microbial Biology, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: Wen-Wei
authors.initials: WW
authors.lastname: Liao
authors.affiliation: Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Hargan-Calvopiña
authors.affiliation: Institute of Plant and Microbial Biology, Academia Sinica, Taipei 11529, Taiwan. Electronic address: paoyang@gate.sinica.edu.tw.
authors.forename: Pao-Yang
authors.initials: PY
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Amander T
authors.initials: AT
authors.lastname: Clark
mesh_terms: D001755:Blastocyst / Q000378:metabolism*; D053624:Blastocyst Inner Cell Mass; D019175:DNA Methylation; D004622:Embryo, Mammalian / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D005854:Germ Cells / Q000378:metabolism*; D006801:Humans; D008297:Male