Characterisation of the epigenetic changes during human gonadal primordial germ cells reprogramming
File(s)Eguizabal et al_final merged.pdf (164.38 MB)
Accepted version
Author(s)
Eguizabal, C
Hajkova, P
Izpisua Belmonte, JC
Type
Journal Article
Abstract
Epigenetic reprogramming is a central process during mammalian germline development. Genome-wide DNA demethylation in primordial germ cells (PGCs) is a prerequisite for the erasure of epigenetic memory, preventing the transmission of epimutations to the next generation. Apart from DNA demethylation, germline reprogramming has been shown to entail reprogramming of histone marks and chromatin remodelling. Contrary to other animal models, there is limited information about the epigenetic dynamics during early germ cell development in humans. Here, we provide further characterization of the epigenetic configuration of the early human gonadal PGCs. We show that early gonadal human PGCs are DNA hypomethylated and their chromatin is characterized by low H3K9me2 and high H3K27me3 marks. Similarly to previous observations in mice, human gonadal PGCs undergo dynamic chromatin changes concomitant with the erasure of genomic imprints. Interestingly, and contrary to mouse early germ cells, expression of BLIMP1/PRDM1 persists in through all gestational stages in human gonadal PGCs and is associated with nuclear lysine-specific demethylase-1. Our work provides important additional information regarding the chromatin changes associated with human PGCs development between 6 and 13 weeks of gestation in male and female gonads.
Date Issued
2016-06-30
Date Acceptance
2016-04-29
Citation
Stem cells
ISSN
0250-6793
Publisher
Wiley
Start Page
2418
End Page
2428
Journal / Book Title
Stem cells
Volume
34
Issue
9
Copyright Statement
This is the peer reviewed version of the following article: Eguizabal, C., Herrera, L., De Oñate, L., Montserrat, N., Hajkova, P. and Izpisua Belmonte, J. C. (2016), Characterization of the Epigenetic Changes During Human Gonadal Primordial Germ Cells Reprogramming. STEM CELLS, which has been published in final form at https://dx.doi.org/10.1002/stem.2422. This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving.
Sponsor
Commission of the European Communities
EMBO
Commission of the European Communities
Grant Number
257082
EMBO YIP
648879
Subjects
Epigenetic
Human primordial germ cells
Reprograming
Immunology
06 Biological Sciences
10 Technology
11 Medical And Health Sciences
Publication Status
Published