The potential for early embryonic events to program epigenetic states that influence adult physiology remains an important question in health and development. Using the imprinted Zdbf2 locus as a paradigm for the early programming of phenotypes, we demonstrate here that chromatin changes that occur in the pluripotent embryo can be dispensable for embryogenesis but instead signal essential regulatory information in the adult. The Liz (long isoform of Zdbf2) transcript is transiently expressed in early embryos and embryonic stem cells (ESCs). This transcription locally promotes de novo DNA methylation upstream of the Zdbf2 promoter, which antagonizes Polycomb-mediated repression of Zdbf2. Strikingly, mouse embryos deficient for Liz develop normally but fail to activate Zdbf2 in the postnatal brain and show indelible growth reduction, implying a crucial role for a Liz-dependent epigenetic switch. This work provides evidence that transcription during an early embryonic timeframe can program a stable epigenetic state with later physiological consequences.
This is a preview of subscription content, access via your institution
Open Access articles citing this article.
Conservation and divergence of canonical and non-canonical imprinting in murids
Genome Biology Open Access 14 March 2023
Molecular versatility during pluripotency progression
Nature Communications Open Access 05 January 2023
Distinctive aspects of the placental epigenome and theories as to how they arise
Cellular and Molecular Life Sciences Open Access 26 October 2022
Subscribe to this journal
Receive 12 print issues and online access
$189.00 per year
only $15.75 per issue
Rent or buy this article
Get just this article for as long as you need it
Prices may be subject to local taxes which are calculated during checkout
Gene Expression Omnibus
Borsos, M. & Torres-Padilla, M.E. Building up the nucleus: nuclear organization in the establishment of totipotency and pluripotency during mammalian development. Genes Dev. 30, 611–621 (2016).
Schübeler, D. et al. Genomic targeting of methylated DNA: influence of methylation on transcription, replication, chromatin structure, and histone acetylation. Mol. Cell. Biol. 20, 9103–9112 (2000).
Lee, H.J., Hore, T.A. & Reik, W. Reprogramming the methylome: erasing memory and creating diversity. Cell Stem Cell 14, 710–719 (2014).
Auclair, G., Guibert, S., Bender, A. & Weber, M. Ontogeny of CpG island methylation and specificity of DNMT3 methyltransferases during embryonic development in the mouse. Genome Biol. 15, 545 (2014).
Dhayalan, A. et al. The Dnmt3a PWWP domain reads histone 3 lysine 36 trimethylation and guides DNA methylation. J. Biol. Chem. 285, 26114–26120 (2010).
Baubec, T. et al. Genomic profiling of DNA methyltransferases reveals a role for DNMT3B in genic methylation. Nature 520, 243–247 (2015).
Ooi, S.K. et al. DNMT3L connects unmethylated lysine 4 of histone H3 to de novo methylation of DNA. Nature 448, 714–717 (2007).
Guo, X. et al. Structural insight into autoinhibition and histone H3–induced activation of DNMT3A. Nature 517, 640–644 (2015).
Tanay, A., O'Donnell, A.H., Damelin, M. & Bestor, T.H. Hyperconserved CpG domains underlie Polycomb-binding sites. Proc. Natl. Acad. Sci. USA 104, 5521–5526 (2007).
Brinkman, A.B. et al. Sequential ChIP–bisulfite sequencing enables direct genome-scale investigation of chromatin and DNA methylation cross-talk. Genome Res. 22, 1128–1138 (2012).
Statham, A.L. et al. Bisulfite sequencing of chromatin immunoprecipitated DNA (BisChIP–seq) directly informs methylation status of histone-modified DNA. Genome Res. 22, 1120–1127 (2012).
Jermann, P., Hoerner, L., Burger, L. & Schübeler, D. Short sequences can efficiently recruit histone H3 lysine 27 trimethylation in the absence of enhancer activity and DNA methylation. Proc. Natl. Acad. Sci. USA 111, E3415–E3421 (2014).
Li, E., Bestor, T.H. & Jaenisch, R. Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell 69, 915–926 (1992).
Okano, M., Bell, D.W., Haber, D.A. & Li, E. DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 99, 247–257 (1999).
O'Carroll, D. et al. The Polycomb-group gene Ezh2 is required for early mouse development. Mol. Cell. Biol. 21, 4330–4336 (2001).
Faust, C., Lawson, K.A., Schork, N.J., Thiel, B. & Magnuson, T. The Polycomb-group gene Eed is required for normal morphogenetic movements during gastrulation in the mouse embryo. Development 125, 4495–4506 (1998).
Pasini, D., Bracken, A.P., Jensen, M.R., Lazzerini Denchi, E. & Helin, K. Suz12 is essential for mouse development and for EZH2 histone methyltransferase activity. EMBO J. 23, 4061–4071 (2004).
Duffié, R. et al. The Gpr1/Zdbf2 locus provides new paradigms for transient and dynamic genomic imprinting in mammals. Genes Dev. 28, 463–478 (2014).
Ferguson-Smith, A.C. Genomic imprinting: the emergence of an epigenetic paradigm. Nat. Rev. Genet. 12, 565–575 (2011).
Proudhon, C. et al. Protection against de novo methylation is instrumental in maintaining parent-of-origin methylation inherited from the gametes. Mol. Cell 47, 909–920 (2012).
Kobayashi, H. et al. Identification of the mouse paternally expressed imprinted gene Zdbf2 on chromosome 1 and its imprinted human homolog ZDBF2 on chromosome 2. Genomics 93, 461–472 (2009).
Kobayashi, H. et al. Imprinted DNA methylation reprogramming during early mouse embryogenesis at the Gpr1–Zdbf2 locus is linked to long cis-intergenic transcription. FEBS Lett. 586, 827–833 (2012).
Greenberg, M.V. & Bourc'his, D. Cultural relativism: maintenance of genomic imprints in pluripotent stem cell culture systems. Curr. Opin. Genet. Dev. 31, 42–49 (2015).
Walter, M., Teissandier, A., Pérez-Palacios, R. & Bourc'his, D. An epigenetic switch ensures transposon repression upon dynamic loss of DNA methylation in embryonic stem cells. eLife 5, e11418 (2016).
Guo, G. et al. Klf4 reverts developmentally programmed restriction of ground state pluripotency. Development 136, 1063–1069 (2009).
Feng, S. et al. Conservation and divergence of methylation patterning in plants and animals. Proc. Natl. Acad. Sci. USA 107, 8689–8694 (2010).
Mikkelsen, T.S. et al. Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature 448, 553–560 (2007).
Marks, H. et al. The transcriptional and epigenomic foundations of ground state pluripotency. Cell 149, 590–604 (2012).
Schoeftner, S. et al. Recruitment of PRC1 function at the initiation of X inactivation independent of PRC2 and silencing. EMBO J. 25, 3110–3122 (2006).
Galonska, C., Ziller, M.J., Karnik, R. & Meissner, A. Ground state conditions induce rapid reorganization of core pluripotency factor binding before global epigenetic reprogramming. Cell Stem Cell 17, 462–470 (2015).
Tsumura, A. et al. Maintenance of self-renewal ability of mouse embryonic stem cells in the absence of DNA methyltransferases Dnmt1, Dnmt3a and Dnmt3b. Genes Cells 11, 805–814 (2006).
Jackson, M. et al. Severe global DNA hypomethylation blocks differentiation and induces histone hyperacetylation in embryonic stem cells. Mol. Cell. Biol. 24, 8862–8871 (2004).
Schmidt, C.S. et al. Global DNA hypomethylation prevents consolidation of differentiation programs and allows reversion to the embryonic stem cell state. PLoS One 7, e52629 (2012).
Liu, X. et al. Distinct features of H3K4me3 and H3K27me3 chromatin domains in pre-implantation embryos. Nature 537, 558–562 (2016).
Zheng, H. et al. Resetting epigenetic memory by reprogramming of histone modifications in mammals. Mol. Cell 63, 1066–1079 (2016).
Jeffery, L. & Nakielny, S. Components of the DNA methylation system of chromatin control are RNA-binding proteins. J. Biol. Chem. 279, 49479–49487 (2004).
Grau, D.J. et al. Compaction of chromatin by diverse Polycomb group proteins requires localized regions of high charge. Genes Dev. 25, 2210–2221 (2011).
Venkatesh, S. & Workman, J.L. Histone exchange, chromatin structure and the regulation of transcription. Nat. Rev. Mol. Cell Biol. 16, 178–189 (2015).
Boulard, M., Edwards, J.R. & Bestor, T.H. FBXL10 protects Polycomb-bound genes from hypermethylation. Nat. Genet. 47, 479–485 (2015).
Blackledge, N.P. et al. Variant PRC1 complex–dependent H2A ubiquitylation drives PRC2 recruitment and Polycomb domain formation. Cell 157, 1445–1459 (2014).
Farcas, A.M. et al. KDM2B links the Polycomb repressive complex 1 (PRC1) to recognition of CpG islands. eLife 1, e00205 (2012).
Wu, X., Johansen, J.V. & Helin, K. Fbxl10/Kdm2b recruits Polycomb repressive complex 1 to CpG islands and regulates H2A ubiquitylation. Mol. Cell 49, 1134–1146 (2013).
Wu, H. et al. Dnmt3a-dependent nonpromoter DNA methylation facilitates transcription of neurogenic genes. Science 329, 444–448 (2010).
Moore, T. & Haig, D. Genomic imprinting in mammalian development: a parental tug-of-war. Trends Genet. 7, 45–49 (1991).
Charalambous, M., da Rocha, S.T. & Ferguson-Smith, A.C. Genomic imprinting, growth control and the allocation of nutritional resources: consequences for postnatal life. Curr. Opin. Endocrinol. Diabetes Obes. 14, 3–12 (2007).
Volkow, N.D., Wang, G.J. & Baler, R.D. Reward, dopamine and the control of food intake: implications for obesity. Trends Cogn. Sci. 15, 37–46 (2011).
Smallwood, S.A. et al. Dynamic CpG island methylation landscape in oocytes and preimplantation embryos. Nat. Genet. 43, 811–814 (2011).
Kobayashi, H. et al. Contribution of intragenic DNA methylation in mouse gametic DNA methylomes to establish oocyte-specific heritable marks. PLoS Genet. 8, e1002440 (2012).
Smith, Z.D. et al. A unique regulatory phase of DNA methylation in the early mammalian embryo. Nature 484, 339–344 (2012).
Sanjana, N.E. et al. A transcription activator–like effector toolbox for genome engineering. Nat. Protoc. 7, 171–192 (2012).
Hsu, P.D. et al. DNA targeting specificity of RNA-guided Cas9 nucleases. Nat. Biotechnol. 31, 827–832 (2013).
Cong, L. et al. Multiplex genome engineering using CRISPR/Cas systems. Science 339, 819–823 (2013).
Luikenhuis, S., Wutz, A. & Jaenisch, R. Antisense transcription through the Xist locus mediates Tsix function in embryonic stem cells. Mol. Cell. Biol. 21, 8512–8520 (2001).
Wang, H. et al. One-step generation of mice carrying mutations in multiple genes by CRISPR/Cas-mediated genome engineering. Cell 153, 910–918 (2013).
Kaneda, M. et al. Essential role for de novo DNA methyltransferase Dnmt3a in paternal and maternal imprinting. Nature 429, 900–903 (2004).
Karimi, M. et al. LUMA (LUminometric Methylation Assay)—a high throughput method to the analysis of genomic DNA methylation. Exp. Cell Res. 312, 1989–1995 (2006).
Bock, C. et al. BiQ Analyzer: visualization and quality control for DNA methylation data from bisulfite sequencing. Bioinformatics 21, 4067–4068 (2005).
Heinz, S. et al. Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol. Cell 38, 576–589 (2010).
We would like to thank members of the Bourc'his laboratory for insightful experimental and conceptual input; E. Heard, R. Margueron, J. Barau and R. Duffié for critical advice on the manuscript; M. Weber for the DNMT3-mutant embryos; and C. Jouhanneau and the Institut Curie Animal Facility for excellent mouse husbandry. High-throughput sequencing was performed by the ICGex NGS platform of the Institut Curie supported by grants from the ANR 'Investissements d'Avenir' program (ANR-10-EQPX-03, Equipex and ANR-10-INBS-09-08, France Génomique Consortium) and from Cancéropôle Île-de-France. The laboratory of D.B. is part of the Laboratoire d'Excellence (LABEX) entitled DEEP (11-LBX0044). This research was supported by grants from the ERC (ERC-Cog EpiRepro) and the ANR (ABS4NGS-ANR-11-BINF-0001). M.V.C.G. was supported by ARC and EMBO (LTF 457-2013) postdoctoral fellowships. J.G. was a recipient of a PhD fellowship from DIM Biotherapy, Île-de-France. M.W. was the recipient of a PhD fellowship from the École Polytechnique.
The authors declare no competing financial interests.
Integrated supplementary information
Supplementary Figure 1 Liz/Zdbf2 dynamics in vivo and in vitro.
(a) Schematic of Liz/Zdbf2 regulation during early development. Summary from Duffié et al.18. Liz transcript initiates from the unmethylated paternal gDMR in the preimplantation embryo. After implantation, Liz expression is turned off and the gDMR is methylated on both alleles. From this stage on, DNA methylation is present at the sDMR and Zdbf2 is expressed from its canonical promoter on the same allele from which Liz was previously expressed, i.e., the paternal allele. Filled circles represent methylated CpGs, and unfilled circles represent unmethylated CpGs. (b) BS–pyro data measured in Figure 1d and split into individual CpGs at the gDMR (left; 10 CpGs) and the sDMR (right; 7 CpGs). The CpGs within the clones analyzed in Figure 1c are depicted in red. Data are shown as means ± s.e.m. from two cell culture replicates. (c) RT–qPCR analysis of Liz expression in E3.5 blastocysts and in day 2 EpiLCs. Values relative to the Hprt1 normalizer are similar. Data are shown as means ± s.e.m. from two blastocyst pools and four cell culture replicates.
Supplementary Figure 2 Characterization of the Gpr1–/– cell line.
(a) Schematic of the homozygous Gpr1-mutant cell line generated on the E14 background. The size and genomic coordinates (in brackets) of the deletion carried by each allele are indicated. The positions of the CRISPR sgRNAs (L, left; R, right) around Gpr1 exon 1 are depicted in red. (b) RT–qPCR analysis shows marked depletion of Gpr1 (left) with little effect on Liz (right) expression upon EpiLC differentiation of Gpr1–/– cells in comparison to E14 wild-type cells. The spliced form of Liz was measured here; similar results were obtained with the unspliced form (data not shown). (c) BS–Pyro analysis of the gDMR (left) and sDMR (right) indicates normal kinetics of DNA methylation in these regions upon differentiation in the absence of Gpr1. Data are shown as means ± s.e.m. from two cell culture replicates.
Supplementary Figure 3 Characterization of the ΔLiz and Liz::2×STOP mutant cell lines.
(a) Schematic of the homozygous ∆Liz cell line generated on the E14 background. The size and genomic coordinates (in brackets) of the deletion carried by each allele are indicated. The positions of the TALEN guides (L, left; R, right) around Liz exon 1 are displayed in red. (b) NanoString custom set data representing expression of active Dnmt genes in wild-type and ΔLiz cells across differentiation. (c) NanoString custom set data representing expression of selected pluripotency genes in wild-type and ΔLiz cells across differentiation. (d) Schematic of the 2× polyadenylation cassette inserted downstream of the first exon of Liz by homology-dependent repair. The selectable marker was removed by transient expression of Cre. (e) RT–qPCR measures at the first exon of Liz across differentiation. Transcription initiation is not affected by the presence of the 2×STOP cassette. Data are shown as means ± s.e.m. from three cell culture replicates for b and c and from two replicates for e.
Supplementary Figure 4 Characterization of H3K36me3 regulation and role at the Liz/Zdbf2 locus.
(a) H3K36me3 ChIP–qPCR in wild-type and ΔLiz cell lines at day 2 of EpiLC differentiation. In the absence of Liz, H3K36me3 is depleted along the path of Liz transcription (Liz intron 2, intergenic CGI, sDMR, Zdbf2 promoter, and Zdbf2 gene body). Data are presented as the percentage of input; control loci are indicated on the right. (b) Schematic of the homozygous Setd2–/– cell line generated on the E14 background. The size and genomic coordinates (in brackets) of the deletion carried by each allele are indicated. The positions of the CRISPR sgRNAs (L, left; R, right) around Setd2 exon 3 are displayed in red. (c) Immunoblot showing that global H3K36me3 levels are drastically reduced in Setd2–/– as compared to wild-type ESCs. (d) RT–qPCR analysis of spliced Liz shows normal kinetics of expression upon differentiation of Setd2–/– EpiLCs. (e) ChIP–qPCR analysis indicates a marked depletion of H3K36me3 levels along the path of Liz in Setd2–/– as compared to wild-type ESCs. Data are presented as the percentage of input; control loci are indicated on the right. (f) BS–pyro analysis of the gDMR (top) and sDMR (bottom) in the Setd2–/– line across EpiLC differentiation. DNA methylation is not affected at the final time point, despite a slight delay at day 2 in the sDMR region. *P ≤ 0.05. (g) BS–pyro analysis of the gDMR (top) and sDMR (bottom) from limb buds of E11.5 embryos. We analyzed Dnmt3a–/– and Dnmt3b–/– embryos along with their respective wild-type littermates. The gDMR is around 20% less methylated in Dnmt3a–/– and Dnmt3b–/– embryos, indicating partial redundancy of DNMT3A and DNMT3B. In contrast, the sDMR is normally methylated in both Dnmt3a–/– and Dnmt3b–/– embryos, highlighting complete redundancy of these two enzymes at this locus. *P ≤ 0.05. Data are shown as means ± s.e.m. from two cell culture replicates for a and d–f and from two mouse embryos for each genotype in g.
Supplementary Figure 5 Role of Polycomb at the Liz/Zdbf2 locus.
(a) Screenshots of H3K27me3 ChIP–seq tracks in wild-type and ΔLiz ESCs grown in 2i+vitC medium. While H3K27me3 is enriched over the Liz/Zdbf2 sDMR in comparison to surrounding regions in wild type (blue), the absolute levels are lower than at typical Polycomb targets (Pax5, Pax9 and Gata6), which are enriched in CGIs. In contrast, H3K27me3 enrichment at the sDMR increases to similar levels as seen for Polycomb targets in ΔLiz ESCs (red). This suggests that basal Liz transcription before induction of EpiLC differentiation already competes with Polycomb occupancy. The positions of CGIs are highlighted in green. The y axis for the H3K27me3 tracks indicates units of reads per million mapped reads (rpm). (b) H3K27me3 and H3K4me3 ChIP–qPCR analysis of control loci for Figure 3b (left) and Figure 3e (right). Data are shown as means ± s.e.m. from three (left) and two (right) cell culture replicates. (c) LUMA quantification of global CpG methylation. Even with prolonged culture in 2i+vitC medium, global methylation levels remain high in Eed–/– ESCs at day 0, in single-knockout Eed–/– or double-knockout ΔLiz; Eed–/– cells, relative to their wild-type counterparts, E14 and J1, respectively. Data are shown as means ± s.e.m. from two cell culture replicates. (d) BS–pyro analysis of CpG methylation of the sDMR in Eed-mutant cell lines upon EpiLC differentiation. As with the global genome in c, DNA methylation remains high at the sDMR in Eed-mutant ESCs in 2i+vitC medium (day 0). At day 4 of EpiLC differentiation, global genomic methylation levels were identical for the four cell lines. The time course is interrupted at day 4, as Eed-mutant cells die after this time point. Data are shown as means ± s.e.m. from two to four cell culture replicates. (e) Schematic of the homozygous Eed–/– cell line generated on the ΔLiz background. The size and genomic coordinates (in brackets) of the deletion carried by each allele are indicated. The positions of the sgRNAs (L, left; R, right) around Eed exon 6 are displayed in red. (f) Immunoblotting for EED and H3K27me3 in Eed–/– cell lines. There was no detectable protein and corresponding histone marks in either homozygous line, indicating proper null mutations.
Supplementary Figure 6 Characterization of DNMT triple-knockout EpiLC differentiation.
(a) NanoString custom set data representing expression of selected pluripotency genes in DNMT triple-knockout cells across EpiLC differentiation. Despite lack of DNA methylation, these cells exhibit similar dynamics as wild-type cells (J1). Data are shown as means ± s.e.m. from three cell culture replicates. (b) Representative images of wild-type and DNMT triple-knockout EpiLCs at day 5. There are few, if any, differences at the morphological level. (c) BS–pyro analysis of the gDMR and sDMR confirms no DNA methylation in DNMT triple-knockout cells upon EpiLC differentiation. Data are shown as means ± s.e.m. from three cell culture replicates. (d) H3K27me3 ChIP–qPCR analysis of control loci for Figure 4c. Data are shown as means ± s.e.m. from two cell culture replicates.
Supplementary Figure 7 Generation of Liz paternal-knockout mice and the regulatory effect on Zdbf2.
(a) Schematic of the Liz deletions generated in vivo. The size and genomic coordinates (in brackets) of the deletion carried by the two independent founders (393 and 403) are indicated. The positions of the sgRNAs (L, left; R, right) around Liz exon 1 are displayed in red. (b) sDMR DNA methylation analysis performed by BS–pyro as in Figure 5b, but with E9.5 progenies from the independent founder line 403. Both founder deletions resulted in the same DNA methylation phenotype. n is the number of embryos analyzed. Data are shown as means ± s.e.m. from n embryos. (c) Bisulfite cloning and sequencing shows nearly complete lack of DNA methylation at the sDMR in Liz paternal-knockout embryos at E9.5 (line 393), in comparison to wild-type littermates. (d) Zdbf2 RT–qPCR analysis performed as in Figure 5c, but with E9.5 progenies from the independent founder line 403. n is the number of embryos analyzed. Data are shown as means ± s.e.m. from n embryos. (e) BS–pyro analysis as performed in Figure 5d, but in 8-month-old mice. The data demonstrate that the epigenetic setting of sDMR methylation persists upon aging of Liz paternal-knockout mice. (f) RT–qPCR analysis of Zdbf2 expression in a bank of tissues from 6-week-old wild-type mice. Zdbf2 expression is mostly limited to brain tissues, with the hypothalamus exhibiting the highest levels. (g) X-gal staining of wild-type (left) and Zdbf2::lacZ (right) placental sections at E18.5. De, deciduum; Sp, spongiotrophoblast; lab, labyrinth. Top: 10× magnification, scale bars = 100 μm; bottom: 40× magnification, scale bars = 25 μm. (h) RT–qPCR analysis as performed in Figure 5g, but in 8-month-old mice. The data demonstrate that the effect on Zdbf2 expression persists in aged Liz paternal-knockout mice. ****P ≤ 0.0001, ***P ≤ 0.001, **P ≤ 0.01, *P ≤ 0.05. Data are shown as means ± s.e.m. from three (f) or two (e,g) mice.
Supplementary Figure 8 Phenotypic characterization of Liz knockout mice.
(a) Genotype ratios observed at birth (heterozygotes and wild type) upon paternal and maternal transmission of the Liz deletion after three backcrosses of the 393 line. Numbers of counted animals of each genotype are given on the histograms. (b) Sex ratios observed at birth among Liz heterozygotes upon paternal (PatKO) and maternal (MatKO) transmission of the deletion after three backcrosses of the 393 line. Numbers of counted animals of each sex are given on the histograms. (c) Individual organ weights plotted as the percentage of total body weight in Liz paternal-knockout mice in comparison to wild-type littermates. Data are shown as means ± s.e.m. from n individuals. (d,e) Growth curves as in Figure 6b and Figure 6c, respectively, but comparing Liz maternal-knockout mice with their wild-type littermates. The Liz deletion behaves as a silent mutation upon maternal transmission: there is no growth-related phenotype in Liz maternal-knockout progenies. Between 15 and 30 mice were analyzed per genotype, depending on age and sex. Data are shown as means ± s.e.m. (f) Scatterplot comparing the body weight of wild-type and Liz paternal-knockout embryos (top) and placentae (bottom) at E18.5. Each point represents one individual. n is the number of embryos or placentae analyzed. (g) Hematoxylin and eosin staining of wild-type and Liz paternal-knockout placentae at E18.5. De, deciduum; Sp, spongiotrophoblast; Lab, labyrinth. Top: 2× magnification, scale bars = 500 μm; bottom: 10× magnification, scale bars = 100 μm.
Supplementary Text and Figures
Supplementary Figures 1–8 and Supplementary Tables 1 and 2. (PDF 1684 kb)
Rights and permissions
About this article
Cite this article
Greenberg, M., Glaser, J., Borsos, M. et al. Transient transcription in the early embryo sets an epigenetic state that programs postnatal growth. Nat Genet 49, 110–118 (2017). https://doi.org/10.1038/ng.3718
This article is cited by
Conservation and divergence of canonical and non-canonical imprinting in murids
Genome Biology (2023)
Molecular versatility during pluripotency progression
Nature Communications (2023)
Distinctive aspects of the placental epigenome and theories as to how they arise
Cellular and Molecular Life Sciences (2022)
Epigenetics of pregnancy: looking beyond the DNA code
Journal of Assisted Reproduction and Genetics (2022)
Repression of germline genes by PRC1.6 and SETDB1 in the early embryo precedes DNA methylation-mediated silencing
Nature Communications (2021)