Metabolic control of DNA methylation in naive pluripotent cells.

Animals Blastocyst / physiology Cell Differentiation Cells, Cultured DNA (Cytosine-5-)-Methyltransferases / genetics DNA Methylation / physiology DNA Methyltransferase 3A Embryonic Stem Cells / metabolism Gene Expression Regulation Histones / metabolism Ketoglutaric Acids / metabolism Leukemia Inhibitory Factor / metabolism Mice, Knockout Nerve Tissue Proteins / genetics Otx Transcription Factors / genetics Pluripotent Stem Cells / metabolism Promoter Regions, Genetic STAT3 Transcription Factor / genetics DNA Methyltransferase 3B

Journal

Nature genetics
ISSN: 1546-1718
Titre abrégé: Nat Genet
Pays: United States
ID NLM: 9216904

Informations de publication

Date de publication:
02 2021
Historique:
received: 01 08 2019
accepted: 17 12 2020
pubmed: 3 2 2021
medline: 5 3 2021
entrez: 2 2 2021
Statut: ppublish

Résumé

Naive epiblast and embryonic stem cells (ESCs) give rise to all cells of adults. Such developmental plasticity is associated with genome hypomethylation. Here, we show that LIF-Stat3 signaling induces genomic hypomethylation via metabolic reconfiguration. Stat3

Identifiants

DOI: 10.1038/s41588-020-00770-2 PMID: 33526924 PMC: PMC7116828
pubmed: 33526924
doi: 10.1038/s41588-020-00770-2
pii: 10.1038/s41588-020-00770-2
pmc: PMC7116828
mid: EMS114658
doi:

Substances chimiques

Dnmt3a protein, mouse 0
Histones 0
Ketoglutaric Acids 0
Leukemia Inhibitory Factor 0
Lif protein, mouse 0
Nerve Tissue Proteins 0
Otx Transcription Factors 0
Otx3 protein, mouse 0
STAT3 Transcription Factor 0
Stat3 protein, mouse 0
histone H3 trimethyl Lys4 0
DNA (Cytosine-5-)-Methyltransferases EC 2.1.1.37
DNA Methyltransferase 3A EC 2.1.1.37

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

215-229

Subventions

Organisme : Medical Research Council
ID : MC_PC_17230
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : RG77233
Pays : United Kingdom

Références

Ito, S. et al. Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification. Nature 466, 1129–1133 (2010).
pubmed: 20639862 pmcid: 3491567 doi: 10.1038/nature09303
Ito, S. et al. Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine. Science 333, 1300–1303 (2011).
pubmed: 21778364 pmcid: 3495246 doi: 10.1126/science.1210597
Messerschmidt, D. M., Knowles, B. B. & Solter, D. DNA methylation dynamics during epigenetic reprogramming in the germline and preimplantation embryos. Genes Dev. 28, 812–828 (2014).
pubmed: 24736841 pmcid: 4003274 doi: 10.1101/gad.234294.113
Monk, M., Boubelik, M. & Lehnert, S. Temporal and regional changes in DNA methylation in the embryonic, extraembryonic and germ cell lineages during mouse embryo development. Development 99, 371–382 (1987).
pubmed: 3653008 doi: 10.1242/dev.99.3.371
Smith, Z. D. et al. A unique regulatory phase of DNA methylation in the early mammalian embryo. Nature 484, 339–344 (2012).
pubmed: 22456710 pmcid: 3331945 doi: 10.1038/nature10960
Ishida, M. & Moore, G. E. The role of imprinted genes in humans. Mol. Aspects Med. 34, 826–840 (2013).
pubmed: 22771538 doi: 10.1016/j.mam.2012.06.009
Boroviak, T. et al. Lineage-specific profiling delineates the emergence and progression of naive pluripotency in mammalian embryogenesis. Dev. Cell 35, 366–382 (2015).
pubmed: 26555056 pmcid: 4643313 doi: 10.1016/j.devcel.2015.10.011
Do, D. V. et al. A genetic and developmental pathway from STAT3 to the OCT4–NANOG circuit is essential for maintenance of ICM lineages in vivo. Genes Dev. 27, 1378–1390 (2013).
pubmed: 23788624 pmcid: 3701193 doi: 10.1101/gad.221176.113
Martello, G., Bertone, P. & Smith, A. Identification of the missing pluripotency mediator downstream of leukaemia inhibitory factor. EMBO J. 32, 2561–2574 (2013).
pubmed: 23942233 pmcid: 3791366 doi: 10.1038/emboj.2013.177
Mohammed, H. et al. Single-cell landscape of transcriptional heterogeneity and cell fate decisions during mouse early gastrulation. Cell Rep. 20, 1215–1228 (2017).
pubmed: 28768204 pmcid: 5554778 doi: 10.1016/j.celrep.2017.07.009
Ye, S., Li, P., Tong, C. & Ying, Q. L. Embryonic stem cell self-renewal pathways converge on the transcription factor Tfcp2l1. EMBO J. 32, 2548–2560 (2013).
pubmed: 23942238 pmcid: 3791365 doi: 10.1038/emboj.2013.175
Boroviak, T. & Nichols, J. Primate embryogenesis predicts the hallmarks of human naive pluripotency. Development 144, 175–186 (2017).
pubmed: 28096211 pmcid: 5430762 doi: 10.1242/dev.145177
Ying, Q.-L. et al. The ground state of embryonic stem cell self-renewal. Nature 453, 519–523 (2008).
pubmed: 18497825 pmcid: 5328678 doi: 10.1038/nature06968
Ficz, G. et al. FGF signaling inhibition in ESCs drives rapid genome-wide demethylation to the epigenetic ground state of pluripotency. Cell Stem Cell 13, 351–359 (2013).
pubmed: 23850245 pmcid: 3765959 doi: 10.1016/j.stem.2013.06.004
Habibi, E. et al. Whole-genome bisulfite sequencing of two distinct interconvertible DNA methylomes of mouse embryonic stem cells. Cell Stem Cell 13, 360–369 (2013).
pubmed: 23850244 doi: 10.1016/j.stem.2013.06.002
Hackett, J. A. et al. Synergistic mechanisms of DNA demethylation during transition to ground-state pluripotency. Stem Cell Rep. 1, 518–531 (2013).
doi: 10.1016/j.stemcr.2013.11.010
Leitch, H. G. et al. Naive pluripotency is associated with global DNA hypomethylation. Nat. Struct. Mol. Biol. 20, 311–316 (2013).
pubmed: 23416945 pmcid: 3591483 doi: 10.1038/nsmb.2510
Smith, A. G. et al. Inhibition of pluripotential embryonic stem cell differentiation by purified polypeptides. Nature 336, 688–690 (1988).
pubmed: 3143917 doi: 10.1038/336688a0
Carbognin, E., Betto, R. M., Soriano, M. E., Smith, A. G. & Martello, G. Stat3 promotes mitochondrial transcription and oxidative respiration during maintenance and induction of naive pluripotency. EMBO J. 35, 618–634 (2016).
pubmed: 26903601 pmcid: 4801951 doi: 10.15252/embj.201592629
Gough, D. J. et al. Mitochondrial STAT3 supports Ras-dependent oncogenic transformation. Science 324, 1713–1716 (2009).
pubmed: 19556508 pmcid: 2840701 doi: 10.1126/science.1171721
Wegrzyn, J. et al. Function of mitochondrial Stat3 in cellular respiration. Science 323, 793–797 (2009).
pubmed: 19131594 pmcid: 2758306 doi: 10.1126/science.1164551
Lu, C. & Thompson, C. B. Metabolic regulation of epigenetics. Cell Metab. 16, 9–17 (2012).
pubmed: 22768835 pmcid: 3392647 doi: 10.1016/j.cmet.2012.06.001
Dawlaty, M. M. et al. Loss of Tet enzymes compromises proper differentiation of embryonic stem cells. Dev. Cell 29, 102–111 (2014).
pubmed: 24735881 pmcid: 4035811 doi: 10.1016/j.devcel.2014.03.003
von Meyenn, F. et al. Impairment of DNA methylation maintenance is the main cause of global demethylation in naive embryonic stem cells. Mol. Cell 62, 848–861 (2016).
doi: 10.1016/j.molcel.2016.04.025
Martello, G. et al. Esrrb is a pivotal target of the Gsk3/Tcf3 axis regulating embryonic stem cell self-renewal. Cell Stem Cell 11, 491–504 (2012).
pubmed: 23040478 pmcid: 3465555 doi: 10.1016/j.stem.2012.06.008
Yamane, M., Ohtsuka, S., Matsuura, K., Nakamura, A. & Niwa, H. Overlapping functions of Krüppel-like factor family members: targeting multiple transcription factors to maintain the naive pluripotency of mouse embryonic stem cells. Development 145, dev162404 (2018).
Elhamamsy, A. R. Role of DNA methylation in imprinting disorders: an updated review. J. Assist. Reprod. Genet. 34, 549–562 (2017).
pubmed: 28281142 pmcid: 5427654 doi: 10.1007/s10815-017-0895-5
Ferguson-Smith, A. C. Genomic imprinting: the emergence of an epigenetic paradigm. Nat. Rev. Genet. 12, 565–575 (2011).
pubmed: 21765458 doi: 10.1038/nrg3032
Hackett, J. A., Kobayashi, T., Dietmann, S. & Surani, M. A. Activation of lineage regulators and transposable elements across a pluripotent spectrum. Stem Cell Rep. 8, 1645–1658 (2017).
doi: 10.1016/j.stemcr.2017.05.014
Sánchez-Castillo, M. et al. CODEX: a next-generation sequencing experiment database for the haematopoietic and embryonic stem cell communities. Nucleic Acids Res. 43, D1117–D1123 (2015).
pubmed: 25270877 doi: 10.1093/nar/gku895
Matsuda, T. et al. STAT3 activation is sufficient to maintain an undifferentiated state of mouse embryonic stem cells. EMBO J. 18, 4261–4269 (1999).
pubmed: 10428964 pmcid: 1171502 doi: 10.1093/emboj/18.15.4261
Tang, Y. et al. Jak/Stat3 signaling promotes somatic cell reprogramming by epigenetic regulation. Stem Cells 30, 2645–2656 (2012).
pubmed: 22968989 doi: 10.1002/stem.1225
Peron, M. et al. Mitochondrial STAT3 regulates proliferation of tissue stem cells. Preprint at bioRxiv https://doi.org/10.1101/2020.07.17.208264 (2020).
Carey, B. W., Finley, L. W. S., Cross, J. R., Allis, C. D. & Thompson, C. B. Intracellular α-ketoglutarate maintains the pluripotency of embryonic stem cells. Nature 518, 413–416 (2015).
pubmed: 25487152 doi: 10.1038/nature13981
Hou, P. et al. Intermediary metabolite precursor dimethyl-2-ketoglutarate stabilizes hypoxia-inducible factor-1α by inhibiting prolyl-4-hydroxylase PHD2. PLoS ONE 9, e113865 (2014).
pubmed: 25420025 pmcid: 4242664 doi: 10.1371/journal.pone.0113865
Xu, Y. et al. Genome-wide regulation of 5hmC, 5mC, and gene expression by Tet1 hydroxylase in mouse embryonic stem cells. Mol. Cell 42, 451–464 (2011).
pubmed: 21514197 pmcid: 3099128 doi: 10.1016/j.molcel.2011.04.005
Chen, T., Ueda, Y., Dodge, J. E., Wang, Z. & Li, E. Establishment and maintenance of genomic methylation patterns in mouse embryonic stem cells by Dnmt3a and Dnmt3b. Mol. Cell. Biol. 23, 5594–5605 (2003).
pubmed: 12897133 pmcid: 166327 doi: 10.1128/MCB.23.16.5594-5605.2003
Tischler, J. et al. Metabolic regulation of pluripotency and germ cell fate through α-ketoglutarate. EMBO J. 38, e99518 (2018).
pubmed: 30257965 pmcid: 6315289
Laukka, T. et al. Fumarate and succinate regulate expression of hypoxia-inducible genes via TET enzymes. J. Biol. Chem. 291, 4256–4265 (2016).
pubmed: 26703470 doi: 10.1074/jbc.M115.688762
Xiao, M. et al. Inhibition of α-KG-dependent histone and DNA demethylases by fumarate and succinate that are accumulated in mutations of FH and SDH tumor suppressors. Genes Dev. 26, 1326–1338 (2012).
pubmed: 22677546 pmcid: 3387660 doi: 10.1101/gad.191056.112
Teslaa, T. & Teitell, M. A. Pluripotent stem cell energy metabolism: an update. EMBO J. 34, 138–153 (2015).
pubmed: 25476451 doi: 10.15252/embj.201490446
Nishiyama, A. et al. Systematic repression of transcription factors reveals limited patterns of gene expression changes in ES cells. Sci. Rep. 3, 5–10 (2013).
doi: 10.1038/srep01390
Correa-Cerro, L. S. et al. Generation of mouse ES cell lines engineered for the forced induction of transcription factors. Sci. Rep. 1, 167 (2011).
pubmed: 22355682 pmcid: 3240988 doi: 10.1038/srep00167
Nishiyama, A. et al. Uncovering early response of gene regulatory networks in ESCs by systematic induction of transcription factors. Cell Stem Cell 5, 420–433 (2009).
pubmed: 19796622 pmcid: 2770715 doi: 10.1016/j.stem.2009.07.012
Buecker, C. et al. Reorganization of enhancer patterns in transition from naive to primed pluripotency. Cell Stem Cell 14, 838–853 (2014).
pubmed: 24905168 pmcid: 4491504 doi: 10.1016/j.stem.2014.04.003
Yang, S.-H. et al. Otx2 and Oct4 drive early enhancer activation during embryonic stem cell transition from naive pluripotency. Cell Rep. 7, 1968–1981 (2014).
pubmed: 24931607 pmcid: 4074343 doi: 10.1016/j.celrep.2014.05.037
Pawlak, M. & Jaenisch, R. De novo DNA methylation by Dnmt3a and Dnmt3b is dispensable for nuclear reprogramming of somatic cells to a pluripotent state. Genes Dev. 25, 1035–1040 (2011).
pubmed: 21576263 pmcid: 3093119 doi: 10.1101/gad.2039011
Grabole, N. et al. Prdm14 promotes germline fate and naive pluripotency by repressing FGF signalling and DNA methylation. EMBO Rep. 14, 629–637 (2013).
pubmed: 23670199 pmcid: 3701237 doi: 10.1038/embor.2013.67
Yamaji, M. et al. PRDM14 ensures naive pluripotency through dual regulation of signaling and epigenetic pathways in mouse embryonic stem cells. Cell Stem Cell 12, 368–382 (2013).
pubmed: 23333148 doi: 10.1016/j.stem.2012.12.012
Dan, J. et al. Roles for Tbx3 in regulation of two-cell state and telomere elongation in mouse ES cells. Sci. Rep. 3, 3492 (2013).
pubmed: 24336466 pmcid: 3861804 doi: 10.1038/srep03492
Palamarchuk, A. et al. Tcl1 protein functions as an inhibitor of de novo DNA methylation in B-cell chronic lymphocytic leukemia (CLL). Proc. Natl Acad. Sci. USA 109, 2555–2560 (2012).
pubmed: 22308499 pmcid: 3289317 doi: 10.1073/pnas.1200003109
Acampora, D., Giovannantonio, L. G. D. & Simeone, A. Otx2 is an intrinsic determinant of the embryonic stem cell state and is required for transition to a stable epiblast stem cell condition. Development 140, 43–55 (2013).
pubmed: 23154415 doi: 10.1242/dev.085290
Kalkan, T. et al. Tracking the embryonic stem cell transition from ground state pluripotency. Development 144, 1221–1234 (2017).
pubmed: 28174249 pmcid: 5399622
Koh, K. P. et al. Tet1 and Tet2 regulate 5-hydroxymethylcytosine production and cell lineage specification in mouse embryonic stem cells. Cell Stem Cell 8, 200–213 (2011).
pubmed: 21295276 pmcid: 3134318 doi: 10.1016/j.stem.2011.01.008
Meissner, A. et al. Genome-scale DNA methylation maps of pluripotent and differentiated cells. Nature 454, 766–770 (2008).
pubmed: 18600261 pmcid: 2896277 doi: 10.1038/nature07107
Tahiliani, M. et al. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science 324, 930–935 (2009).
pubmed: 19372391 pmcid: 2715015 doi: 10.1126/science.1170116
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).
pubmed: 16824199 doi: 10.1111/j.1365-2443.2006.00984.x
Zhou, W. et al. HIF1α induced switch from bivalent to exclusively glycolytic metabolism during ESC-to-EpiSC/hESC transition. EMBO J. 31, 2103–2116 (2012).
pubmed: 22446391 pmcid: 3343469 doi: 10.1038/emboj.2012.71
Bourillot, P. Y. et al. Novel STAT3 target genes exert distinct roles in the inhibition of mesoderm and endoderm differentiation in cooperation with Nanog. Stem Cells 27, 1760–1771 (2009).
pubmed: 19544440 doi: 10.1002/stem.110
Niwa, H., Ogawa, K., Shimosato, D. & Adachi, K. A parallel circuit of LIF signalling pathways maintains pluripotency of mouse ES cells. Nature 460, 118–122 (2009).
pubmed: 19571885 doi: 10.1038/nature08113
Boroviak, T., Loos, R., Bertone, P., Smith, A. & Nichols, J. The ability of inner-cell-mass cells to self-renew as embryonic stem cells is acquired following epiblast specification. Nat. Cell Biol. 16, 516–528 (2014).
pubmed: 24859004 pmcid: 4878656 doi: 10.1038/ncb2965
McLaughlin, K. et al. DNA methylation directs polycomb-dependent 3D genome re-organization in naive pluripotency. Cell Rep. 29, 1974–1985 (2019).
pubmed: 31722211 pmcid: 6856714 doi: 10.1016/j.celrep.2019.10.031
Takeda, K. et al. Targeted disruption of the mouse Stat3 gene leads to early embryonic lethality. Proc. Natl Acad. Sci. USA 94, 3801–3804 (1997).
pubmed: 9108058 pmcid: 20521 doi: 10.1073/pnas.94.8.3801
Leeb, M., Dietmann, S., Paramor, M., Niwa, H. & Smith, A. Genetic exploration of the exit from self-renewal using haploid embryonic stem cells. Cell Stem Cell 14, 385–393 (2014).
pubmed: 24412312 pmcid: 3995090 doi: 10.1016/j.stem.2013.12.008
Avalle, L. et al. STAT3 localizes to the ER, acting as a gatekeeper for ER-mitochondrion Ca
pubmed: 30042492 doi: 10.1038/s41418-018-0171-y
Wang, L. et al. JAK/STAT3 regulated global gene expression dynamics during late-stage reprogramming process. BMC Genomics 19, 183 (2018).
pubmed: 29510661 pmcid: 5840728 doi: 10.1186/s12864-018-4507-2
Hwang, I.-Y. et al. Psat1-dependent fluctuations in α-ketoglutarate affect the timing of ESC differentiation. Cell Metab. 24, 494–501 (2016).
pubmed: 27476977 doi: 10.1016/j.cmet.2016.06.014
Zhang, J. et al. LIN28 regulates stem cell metabolism and conversion to primed pluripotency. Cell Stem Cell 19, 66–80 (2016).
pubmed: 27320042 doi: 10.1016/j.stem.2016.05.009
Mullen, A. R. et al. Reductive carboxylation supports growth in tumour cells with defective mitochondria. Nature 481, 385–388 (2012).
doi: 10.1038/nature10642
Choi, J. et al. Prolonged Mek1/2 suppression impairs the developmental potential of embryonic stem cells. Nature 548, 219–223 (2017).
pubmed: 28746311 pmcid: 5905676 doi: 10.1038/nature23274
Yagi, M. et al. Derivation of ground-state female ES cells maintaining gamete-derived DNA methylation. Nature 548, 224–227 (2017).
pubmed: 28746308 doi: 10.1038/nature23286
Gretarsson, K. J. & Hackett, J. A. Dppa2 and Dppa4 counteract de novo methylation to establish a permissive epigenome for development. Nat. Struct. Mol. Biol. 27, 706–716 (2020).
pubmed: 32572256 doi: 10.1038/s41594-020-0445-1
Chen, T., Ueda, Y., Xie, S. & Li, E. A novel Dnmt3a isoform produced from an alternative promoter localizes to euchromatin and its expression correlates with activede novo methylation. J. Biol. Chem. 277, 38746–38754 (2002).
pubmed: 12138111 doi: 10.1074/jbc.M205312200
Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014).
Neri, F., Incarnato, D., Krepelova, A., Parlato, C. & Oliviero, S. Methylation-assisted bisulfite sequencing to simultaneously map 5fC and 5caC on a genome-wide scale for DNA demethylation analysis. Nat. Protoc. 11, 1191–1205 (2016).
pubmed: 27281647 doi: 10.1038/nprot.2016.063
Xi, Y. & Li, W. BSMAP: whole genome bisulfite sequence MAPping program. BMC Bioinform. 10, 232 (2009).
doi: 10.1186/1471-2105-10-232
Akalin, A. et al. methylKit: A comprehensive R package for the analysis of genome-wide DNA methylation profiles. Genome Biol. 13, R87 (2012).
pubmed: 23034086 pmcid: 3491415 doi: 10.1186/gb-2012-13-10-r87
Boroviak, T. et al. Single cell transcriptome analysis of human, marmoset and mouse embryos reveals common and divergent features of preimplantation development. Development 145, dev167833 (2018).
Dobin, A. et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29, 15–21 (2013).
pubmed: 23104886 doi: 10.1093/bioinformatics/bts635
Anders, S., Pyl, P. T. & Huber, W. HTSeq—a Python framework to work with high-throughput sequencing data. Bioinformatics 31, 166–169 (2015).
pubmed: 25260700 doi: 10.1093/bioinformatics/btu638
Anders, S. & Huber, W. Differential expression analysis for sequence count data. Genome Biol. 11, R106 (2010).
pubmed: 20979621 pmcid: 3218662 doi: 10.1186/gb-2010-11-10-r106
Lê, S., Josse, J. & Husson, F. FactoMineR: an R package for multivariate analysis. J. Stat. Softw. 25, 1–18 (2008).
doi: 10.18637/jss.v025.i01
Risso, D., Perraudeau, F., Gribkova, S., Dudoit, S. & Vert, J.-P. A general and flexible method for signal extraction from single-cell RNA-seq data. Nat. Commun. 9, 284 (2018).
pubmed: 29348443 pmcid: 5773593 doi: 10.1038/s41467-017-02554-5
Gong, T. & Szustakowski, J. D. DeconRNASeq: a statistical framework for deconvolution of heterogeneous tissue samples based on mRNA-Seq data. Bioinformatics 29, 1083–1085 (2013).
pubmed: 23428642 doi: 10.1093/bioinformatics/btt090
Rappsilber, J., Ishihama, Y. & Mann, M. Stop and go extraction tips for matrix-assisted laser desorption/ionization, nanoelectrospray, and LC/MS sample pretreatment in proteomics. Anal. Chem. 75, 663–670 (2003).
pubmed: 12585499 doi: 10.1021/ac026117i
Michalski, A. et al. Mass spectrometry-based proteomics using Q Exactive, a high-performance benchtop quadrupole Orbitrap mass spectrometer. Mol. Cell. Proteomics 10, M111.011015 (2011).

Auteurs

Riccardo M Betto (RM)

Department of Molecular Medicine, Medical School, University of Padua, Padua, Italy.
ORCID: 0000-0001-5083-0668

Linda Diamante (L)

Department of Molecular Medicine, Medical School, University of Padua, Padua, Italy.
ORCID: 0000-0002-3268-1707

Valentina Perrera (V)

Department of Molecular Medicine, Medical School, University of Padua, Padua, Italy.
Neuroscience Sector, International School for Advanced Studies (SISSA), Trieste, Italy.

Matteo Audano (M)

Department of Pharmacological and Biomolecular Sciences (DiSFeB), University of Milan, Milan, Italy.

Stefania Rapelli (S)

Department of Life Sciences and Systems Biology, University of Turin, Turin, Italy.
Italian Institute for Genomic Medicine (IIGM), Candiolo, Italy.

Andrea Lauria (A)

Department of Life Sciences and Systems Biology, University of Turin, Turin, Italy.
Italian Institute for Genomic Medicine (IIGM), Candiolo, Italy.

Danny Incarnato (D)

Department of Life Sciences and Systems Biology, University of Turin, Turin, Italy.
Department of Molecular Genetics, Groningen Biomolecular Sciences and Biotechnology Institute (GBB), University of Groningen, Groningen, the Netherlands.
Department of Molecular Genetics, Groningen Biomolecular Sciences and Biotechnology Institute (GBB), University of Groningen, Groningen, the Netherlands.

Mattia Arboit (M)

Department of Molecular Medicine, Medical School, University of Padua, Padua, Italy.

Silvia Pedretti (S)

Department of Pharmacological and Biomolecular Sciences (DiSFeB), University of Milan, Milan, Italy.

Giovanni Rigoni (G)

Department of Biology, University of Padua, Padua, Italy.
Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.

Vincent Guerineau (V)

Université Paris-Saclay, Institut de Chimie des Substances Naturelles, CNRS, Gif-sur-Yvette, France.

David Touboul (D)

Université Paris-Saclay, Institut de Chimie des Substances Naturelles, CNRS, Gif-sur-Yvette, France.

Giuliano Giuseppe Stirparo (GG)

Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
ORCID: 0000-0002-5911-8682

Tim Lohoff (T)

Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
ORCID: 0000-0001-9333-842X

Thorsten Boroviak (T)

Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
Centre for Trophoblast Research, University of Cambridge, Cambridge, UK.
Wellcome Trust-Medical Research Council Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, UK.
ORCID: 0000-0001-8703-8949

Paolo Grumati (P)

Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy.

Maria E Soriano (ME)

Department of Biology, University of Padua, Padua, Italy.

Jennifer Nichols (J)

Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.
Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
ORCID: 0000-0002-8650-1388

Nico Mitro (N)

Department of Pharmacological and Biomolecular Sciences (DiSFeB), University of Milan, Milan, Italy. nico.mitro@unimi.it.
ORCID: 0000-0002-5000-3619

Salvatore Oliviero (S)

Department of Life Sciences and Systems Biology, University of Turin, Turin, Italy. salvatore.oliviero@unito.it.
Italian Institute for Genomic Medicine (IIGM), Candiolo, Italy. salvatore.oliviero@unito.it.
ORCID: 0000-0002-3405-765X

Graziano Martello (G)

Department of Molecular Medicine, Medical School, University of Padua, Padua, Italy. graziano.martello@unipd.it.
Department of Biology, University of Padua, Padua, Italy. graziano.martello@unipd.it.
ORCID: 0000-0001-5520-085X

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Metabolic control of DNA methylation in naive...
questionsmedicales.fr › Structures de l'embryon › Embryon de mammifère › Blastocyste › Metabolic control of DNA methylation in naive...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Différenciation cellulaire › Metabolic control of DNA methylation in naive...
questionsmedicales.fr › Cellules › Cellules cultivées › Metabolic control of DNA methylation in naive...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Transferases › One-carbon group transferases › Methyltransferases › DNA modification methylases › DNA-Cytosine Methylases › DNA (cytosine-5-)-methyltransferase › Metabolic control of DNA methylation in naive...
questionsmedicales.fr › Phénomènes génétiques › Méthylation de l'ADN › Metabolic control of DNA methylation in naive...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Transferases › One-carbon group transferases › Methyltransferases › DNA modification methylases › DNA-Cytosine Methylases › DNA (cytosine-5-)-methyltransferase › DNA methyltransferase 3A › Metabolic control of DNA methylation in naive...
questionsmedicales.fr › Cellules › Cellules souches › Cellules souches pluripotentes › Cellules souches embryonnaires › Metabolic control of DNA methylation in naive...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Metabolic control of DNA methylation in naive...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Nucléoprotéines › Histone › Metabolic control of DNA methylation in naive...
questionsmedicales.fr › Composés chimiques organiques › Acides carboxyliques › Cétoacides › Acides cétoglutariques › Metabolic control of DNA methylation in naive...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Facteur inhibiteur de la leucémie › Metabolic control of DNA methylation in naive...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › Souris knockout › Metabolic control of DNA methylation in naive...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de tissu nerveux › Metabolic control of DNA methylation in naive...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteurs de transcription Otx › Metabolic control of DNA methylation in naive...
questionsmedicales.fr › Cellules › Cellules souches › Cellules souches pluripotentes › Metabolic control of DNA methylation in naive...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Gènes › Composants de gène › Éléments de régulation transcriptionnelle › Régions promotrices (génétique) › Metabolic control of DNA methylation in naive...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteurs de transcription STAT › Facteur de transcription STAT-3 › Metabolic control of DNA methylation in naive...