Chromatin modifications during the maternal to zygotic transition (MZT)

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R-HSA-9821002
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Homo sapiens
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Chromatin modifications during the maternal to zygotic transition (MZT)
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Chromatin in the zygotic pronuclei transitions to a more open and accessible conformation by DNA demethylation and changes to histone modifications. As development proceeds through the cleavage stages to the blastocyst, chromatin continues to become more accessible until DNA methylation and a more restrictive chromatin conformation are re-established after implantation of the embryo in the uterus.
In the oocyte, H3K9me2 produced by EHMT2 (G9a, KMT1C) and H3K9me3 produced by SETDB1 (KMT1E) are transmitted to the female pronucleus of the zygote and protect maternal DNA from active demethylation (inferred from mouse zygotes in Zeng et al. 2019, reviewed in de Macedo et al. 2021). DPPA3 binds H3K9me2, preventing the 5-methylcytosine oxidase TET3 from being recruited to chromatin (inferred from mouse homologs in Nakamura et al. 2007, Wossidlo et al. 2011, Nakamura et al. 2012). DPPA3 also displaces UHRF1 from chromatin, preventing the maintenance DNA methylase DNMT1 from being recruited to chromatin and thus allowing passive DNA demethylation to occur in the female genome (inferred from mouse homologs in Funaki et al. 2014, Li et al. 2018, Du et al. 2019, Mulholland et al. 2020).
In the male pronucleus of the zygote, AICDA (AID) deaminates cytosine residues and long patch repair replaces the mismatches and adjacent 5-methylcytidine residues with cytidine (Santos et al. 2013, Franchini et al. 2014). After this initial demethylation, TET3 is recruited to chromatin by METTL23 and STGP4 (GSE) (inferred from mouse homologs in Hatanaka et al. 2017) where it oxidizes remaining 5-methylcytidine to 5-hydroxymethylcytidine, which is removed by base excision repair and replaced with cytidine (inferred from mouse homologs in Gu et al. 2011, Iqbal et al. 2011, Wossidlo et al. 2011, Santos et al. 2013, Amouroux et al. 2016, Hatanaka et al. 2017).
The repressive mark H3K27me3 decreases in 2-cell embryos near developmentally related genes (Xia et al. 2019). The H3K27me3 demethylases KDM6B (inferred from bovine embryos in Chung et al. 2017, Canovas et al. 2012) and KDM6A (inferred from mouse embryos in Bai et al. 2019) appear to play a role in the decrease of H3K27me3, as downregulation of them impairs H3K27me3 loss, zygotic genome activation, and embryonic development. Embryonic development also requires H3K36me3, a permissive mark located in transcribed gene bodies that is produced in the oocyte by SETD2 (inferred from mouse embryos in Xu et al. 2019).
In mouse oocytes, H3K4me3 occurs in unusually broad regions that span genes Dahl et al. 2016, Zhang et al. 2016). These broad regions persist in the zygote and into the 2-cell stage. In the late 2-cell stage the more usual patterns of H3K4me3 are established as sharp peaks of H3K4me3 near the transcription start sites and stop sites of genes. The histone methyltransferase KMT2B is at least partly responsible for establishing the broad regions of H3K4me3 in the oocyte and the histone demethylases KDM5B and KDM5A remove the broad H3K4me3 in the late 2-cell stage embryo (inferred from mouse homologs in Dahl et al. 2016, reviewed in Eckerseley-Maslin et al. 2018).
In human oocytes and zygotes, however, broad regions of H3K4me3 are not observed across genes but are located across distal, CpG-rich domains which have partial DNA methylation (Xia et al. 2019). At the 8-cell stage, expression of KDM5B increases and the H3K4me3 at the distal domains is lost as zygotic genome activation occurs, suggesting a role for KDM5B in loss of H3K4me3 (Xia et al. 2019).
Literature References
PubMed ID Title Journal Year
17143267 PGC7/Stella protects against DNA demethylation in early embryogenesis

Nakamura, T, Arai, Y, Umehara, H, Masuhara, M, Kimura, T, Taniguchi, H, Sekimoto, T, Ikawa, M, Yoneda, Y, Okabe, M, Tanaka, S, Shiota, K, Nakano, T

Nat Cell Biol 2007
28930672 Histone H3 Methylated at Arginine 17 Is Essential for Reprogramming the Paternal Genome in Zygotes

Hatanaka, Y, Tsusaka, T, Shimizu, N, Morita, K, Suzuki, T, Machida, S, Satoh, M, Honda, A, Hirose, M, Kamimura, S, Ogonuki, N, Nakamura, T, Inoue, K, Hosoi, Y, Dohmae, N, Nakano, T, Kurumizaka, H, Matsumoto, K, Shinkai, Y, Ogura, A

Cell Rep 2017
31018966 Stella protein facilitates DNA demethylation by disrupting the chromatin association of the RING finger-type E3 ubiquitin ligase UHRF1

Du, W, Dong, Q, Zhang, Z, Liu, B, Zhou, T, Xu, RM, Wang, H, Zhu, B, Li, Y

J Biol Chem 2019
31088968 EHMT2 and SETDB1 protect the maternal pronucleus from 5mC oxidation

Zeng, TB, Han, L, Pierce, N, Pfeifer, GP, Szabó, PE

Proc Natl Acad Sci U S A 2019
34934530 Chromatin role in early programming of embryos

de Macedo, MP, Glanzner, WG, Gutierrez, K, Bordignon, V

Anim Front 2021
29160132 Active H3K27me3 demethylation by KDM6B is required for normal development of bovine preimplantation embryos

Chung, N, Bogliotti, YS, Ding, W, Vilarino, M, Takahashi, K, Chitwood, JL, Schultz, RM, Ross, PJ

Epigenetics 2017
35955697 Control of Maternal-to-Zygotic Transition in Human Embryos and Other Animal Species (Especially Mouse): Similarities and Differences

Tesarik, J

Int J Mol Sci 2022
21407207 5-Hydroxymethylcytosine in the mammalian zygote is linked with epigenetic reprogramming

Wossidlo, M, Nakamura, T, Lepikhov, K, Marques, CJ, Zakhartchenko, V, Boiani, M, Arand, J, Nakano, T, Reik, W, Walter, J

Nat Commun 2011
31040401 SETD2 regulates the maternal epigenome, genomic imprinting and embryonic development

Xu, Q, Xiang, Y, Wang, Q, Wang, L, Brind'Amour, J, Bogutz, AB, Zhang, Y, Zhang, B, Yu, G, Xia, W, Du, Z, Huang, C, Ma, J, Zheng, H, Li, Y, Liu, C, Walker, CL, Jonasch, E, Lefebvre, L, Wu, M, Lorincz, MC, Li, W, Li, L, Xie, W

Nat Genet 2019
22308433 Jumonji domain-containing protein 3 regulates histone 3 lysine 27 methylation during bovine preimplantation development

Canovas, S, Cibelli, JB, Ross, PJ

Proc Natl Acad Sci U S A 2012
24279473 Active demethylation in mouse zygotes involves cytosine deamination and base excision repair

Santos, F, Peat, J, Burgess, H, Rada, C, Reik, W, Dean, W

Epigenetics Chromatin 2013
25025377 Processive DNA demethylation via DNA deaminase-induced lesion resolution

Franchini, DM, Chan, CF, Morgan, H, Incorvaia, E, Rangam, G, Dean, W, Santos, F, Reik, W, Petersen-Mahrt, SK

PLoS One 2014
26751286 De novo DNA methylation drives 5hmC accumulation in mouse zygotes

Amouroux, R, Nashun, B, Shirane, K, Nakagawa, S, Hill, PW, D'Souza, Z, Nakayama, M, Matsuda, M, Turp, A, Ndjetehe, E, Encheva, V, Kudo, NR, Koseki, H, Sasaki, H, Hajkova, P

Nat Cell Biol 2016
30487604 Stella safeguards the oocyte methylome by preventing de novo methylation mediated by DNMT1

Li, Y, Zhang, Z, Chen, J, Liu, W, Lai, W, Liu, B, Li, X, Liu, L, Xu, S, Dong, Q, Wang, M, Duan, X, Tan, J, Zheng, Y, Zhang, P, Fan, G, Wong, J, Xu, GL, Wang, Z, Wang, H, Gao, S, Zhu, B

Nature 2018
31273069 Resetting histone modifications during human parental-to-zygotic transition

Xia, W, Xu, J, Yu, G, Yao, G, Xu, K, Ma, X, Zhang, N, Liu, B, Li, T, Lin, Z, Chen, X, Li, L, Wang, Q, Shi, D, Shi, S, Zhang, Y, Song, W, Jin, H, Hu, L, Bu, Z, Wang, Y, Na, J, Xie, W, Sun, YP

Science 2019
29686419 Dynamics of the epigenetic landscape during the maternal-to-zygotic transition

Eckersley-Maslin, MA, Alda-Catalinas, C, Reik, W

Nat Rev Mol Cell Biol 2018
25280994 Inhibition of maintenance DNA methylation by Stella

Funaki, S, Nakamura, T, Nakatani, T, Umehara, H, Nakashima, H, Nakano, T

Biochem Biophys Res Commun 2014
31595154 Histone Demethylase UTX is an Essential Factor for Zygotic Genome Activation and Regulates Zscan4 Expression in Mouse Embryos

Bai, L, Yang, L, Zhao, C, Song, L, Liu, X, Bai, C, Su, G, Wei, Z, Li, G

Int J Biol Sci 2019
21892189 The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes

Gu, TP, Guo, F, Yang, H, Wu, HP, Xu, GF, Liu, W, Xie, ZG, Shi, L, He, X, Jin, SG, Iqbal, K, Shi, YG, Deng, Z, Szabó, PE, Pfeifer, GP, Li, J, Xu, GL

Nature 2011
33235224 Recent evolution of a TET-controlled and DPPA3/STELLA-driven pathway of passive DNA demethylation in mammals

Mulholland, CB, Nishiyama, A, Ryan, J, Nakamura, R, Yiğit, M, Glück, IM, Trummer, C, Qin, W, Bartoschek, MD, Traube, FR, Parsa, E, Ugur, E, Modic, M, Acharya, A, Stolz, P, Ziegenhain, C, Wierer, M, Enard, W, Carell, T, Lamb, DC, Takeda, H, Nakanishi, M, Bultmann, S, Leonhardt, H

Nat Commun 2020
21321204 Reprogramming of the paternal genome upon fertilization involves genome-wide oxidation of 5-methylcytosine

Iqbal, K, Jin, SG, Pfeifer, GP, Szabó, PE

Proc. Natl. Acad. Sci. U.S.A. 2011
27626382 Allelic reprogramming of the histone modification H3K4me3 in early mammalian development

Zhang, B, Zheng, H, Huang, B, Li, W, Xiang, Y, Peng, X, Ming, J, Wu, X, Zhang, Y, Xu, Q, Liu, W, Kou, X, Zhao, Y, He, W, Li, C, Chen, B, Li, Y, Wang, Q, Ma, J, Yin, Q, Kee, K, Meng, A, Gao, S, Xu, F, Na, J, Xie, W

Nature 2016
27626377 Broad histone H3K4me3 domains in mouse oocytes modulate maternal-to-zygotic transition

Dahl, JA, Jung, I, Aanes, H, Greggains, GD, Manaf, A, Lerdrup, M, Li, G, Kuan, S, Li, B, Lee, AY, Preissl, S, Jermstad, I, Haugen, MH, Suganthan, R, Bjørås, M, Hansen, K, Dalen, KT, Fedorcsak, P, Ren, B, Klungland, A

Nature 2016
22722204 PGC7 binds histone H3K9me2 to protect against conversion of 5mC to 5hmC in early embryos

Nakamura, T, Liu, YJ, Nakashima, H, Umehara, H, Inoue, K, Matoba, S, Tachibana, M, Ogura, A, Shinkai, Y, Nakano, T

Nature 2012
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epigenetic programming in the zygotic pronuclei (0044725)
Authored
May, B  (2022-11-27)
Reviewed
Xie, W  (2023-08-08)
Created
May, B  (2022-11-27)
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