A Unique Gene Regulatory Network Resets the Human Germline Epigenome for Development
Wellcome/MRC Cambridge Stem Cell Institute · University of Cambridge · +5 more institutions
Abstract
Resetting of the epigenome in human primordial germ cells (hPGCs) is critical for development. We show that the transcriptional program of hPGCs is distinct from that in mice, with co-expression of somatic specifiers and naive pluripotency genes TFCP2L1 and KLF4. This unique gene regulatory network, established by SOX17 and BLIMP1, drives comprehensive germline DNA demethylation by repressing DNA methylation pathways and activating TET-mediated hydroxymethylation. Base-resolution methylome analysis reveals progressive DNA demethylation to basal levels in week 5-7 in vivo hPGCs. Concurrently, hPGCs undergo chromatin reorganization, X reactivation, and imprint erasure. Despite global hypomethylation,…
Citation impact
- FWCI
- 32.67
- Percentile
- 100%
- References
- 40
Authors
9- WWWalfred W. C. Tang
Wellcome/MRC Cambridge Stem Cell Institute, University of Cambridge, The Gurdon Institute, Wellcome Trust, Medical Research Council
- SDSabine Dietmann
Wellcome/MRC Cambridge Stem Cell Institute, Medical Research Council
- NINaoko Irie
Wellcome/MRC Cambridge Stem Cell Institute, University of Cambridge, The Gurdon Institute, Wellcome Trust, Medical Research Council
- HGHarry G. Leitch
Wellcome/MRC Cambridge Stem Cell Institute, Medical Research Council
- VIVasileios I. Floros
Wellcome Centre for Mitochondrial Research, Newcastle University
Topics & keywords
- Biology
- Reprogramming
- DNA demethylation
- DNA methylation
- Epigenome
- Epigenetics
- Genetics
- Chromatin