G9a regulates temporal preimplantation developmental program and lineage segregation in blastocyst

Ż̷ylicz, J.; Borensztein, Maud; Wong, Frederick C K; Huang, Yun; Lee, Caroline; Dietmann, Sabine; Surani, M. Azim

doi:10.7554/elife.33361

Cited by 32 publications

(29 citation statements)

References 44 publications

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“…must be epigenetically programed after fertilization to make embryos capable to pursue their normal developmental course (Siklenka et al, 2015;Dahl et al, 2016;Teperek et al, 2016). A variety of epigenetic regulators such as erasers (e.g., KDM1A, KDM4D, KDM7A) and writers (e.g., SETDB1, SUV39H1/H2, G9a) are necessary to properly implement the epigenetic program in embryos (Jullien et al, 2014;Matoba et al, 2014;Golding et al, 2015;Siklenka et al, 2015;Dahl et al, 2016;Eymery et al, 2016;Zhang et al, 2016;Dumdie et al, 2018;Zylicz et al, 2018;Rissi et al, 2019). However, much remains to be done to uncover the function and interaction of each epigenetic regulator.…”

Section: Discussionmentioning

confidence: 99%

Histone Lysine Demethylases KDM5B and KDM5C Modulate Genome Activation and Stability in Porcine Embryos

Glanzner

Gutierrez

Rissi

et al. 2020

Front. Cell Dev. Biol.

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The lysine demethylases KDM5B and KDM5C are highly, but transiently, expressed in porcine embryos around the genome activation stage. Attenuation of KDM5B and KDM5C mRNA hampered embryo development to the blastocyst stage in fertilized, parthenogenetically activated and nuclear transfer embryos. While KDM5B attenuation increased H3K4me2-3 levels on D3 embryos and H3K4me1-2-3 on D5 embryos, KDM5C attenuation increased H3K9me1 on D3 embryos, and H3K9me1 and H3K4me1 on D5 embryos. The relative mRNA abundance of EIF1AX and EIF2A on D3 embryos, and the proportion of D4 embryos presenting a fluorescent signal for uridine incorporation were severely reduced in both KDM5B-and KDM5Cattenuated compared to control embryos, which indicate a delay in the initiation of the embryo transcriptional activity. Moreover, KDM5B and KDM5C attenuation affected DNA damage response and increased DNA double-strand breaks (DSBs), and decreased development of UV-irradiated embryos. Findings from this study revealed that both KDM5B and KDM5C are important regulators of early development in porcine embryos as their attenuation altered H3K4 and H3K9 methylation patterns, perturbed embryo genome activation, and decreased DNA damage repair capacity.

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Section: Discussionmentioning

confidence: 99%

Histone Lysine Demethylases KDM5B and KDM5C Modulate Genome Activation and Stability in Porcine Embryos

Glanzner

Gutierrez

Rissi

et al. 2020

Front. Cell Dev. Biol.

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“…All experimental protocols were approved by the ethics committee of Institut Curie CEEA-IC118 under the number APAFIS#8812-2017020611033784v2 given by national authority in compliance with the international guidelines. Single-embryo RNA-seq was performed as previously described 35 . Briefly, E3.5 embryos were collected and morphologically assessed to ensure only viable samples were collected.…”

Section: Methodsmentioning

confidence: 99%

SPEN integrates transcriptional and epigenetic control of X-inactivation

Dossin

Pinheiro

Ż̷ylicz

et al. 2020

Nature

166

230

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Summary Xist represents a paradigm for long non-coding RNA function in epigenetic regulation, although how it mediates X-chromosome inactivation (XCI) remains largely unexplained. Multiple Xist -RNA binding proteins have recently been identified, including SPEN 1 – 3 , the loss of which has been associated with deficient XCI at multiple loci 2 – 6 . Here we demonstrate that SPEN is a key orchestrator of XCI in vivo and unravel its mechanism of action. We show that SPEN is essential for initiating gene silencing on the X chromosome in preimplantation mouse embryos and embryonic stem cells. SPEN is dispensable for maintenance of XCI in neural progenitors, although it significantly dampens expression of genes that escape XCI. We show that SPEN is immediately recruited to the X-chromosome upon Xist up-regulation, and is targeted to enhancers and promoters of active genes. SPEN rapidly disengages from chromatin upon gene silencing, implying a need for active transcription to tether it to chromatin. We define SPEN’s SPOC domain as a major effector of SPEN’s gene silencing function, and show that tethering SPOC to Xist RNA is sufficient to mediate gene silencing. We identify SPOC’s protein partners which include NCOR/SMRT, the m6A RNA methylation machinery, the NuRD complex, RNA polymerase II and factors involved in regulation of transcription initiation and elongation. We propose that SPEN acts as a molecular integrator for initiation of XCI, bridging Xist RNA with the transcription machinery as well as nucleosome remodelers and histone deacetylases, at active enhancers and promoters.

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“…G9A), may contribute to essential lineage‐regulation during preimplantation development. Ablation of both maternal and embryonic sources of this protein leads to a failure to repress certain genes at the four‐cell stage, and subsequent dysregulation of lineage segregation at the blastocyst stage (Zylicz et al, 2018). This suggests that the maternally expressed EHMT2 could contribute to the correct programming of later gene expression patterns that contribute to optimum lineage formation, but long‐term studies would be needed to confirm this.…”

Section: Oocyte Histones and Histone Modifiersmentioning

confidence: 99%

Listening to mother: Long‐term maternal effects in mammalian development

Ruebel

Latham

2020

Molecular Reproduction Devel

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The oocyte is a complex cell that executes many crucial and unique functions at the start of each life. These functions are fulfilled by a unique collection of macromolecules and other factors, all of which collectively support meiosis, oocyte activation, and embryo development. This review focuses on the effects of oocyte components on developmental processes that occur after the initial stages of embryogenesis. These include long-term effects on genome function, metabolism, lineage allocation, postnatal progeny health, and even subsequent generations.Factors that regulate chromatin structure, genome programming, and mitochondrial function are elements that contribute to these oocyte functions. K E Y W O R D S chromatin, embryo gene regulation, maternal effect, oocyte 400 |

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G9a regulates temporal preimplantation developmental program and lineage segregation in blastocyst

Cited by 32 publications

References 44 publications

Histone Lysine Demethylases KDM5B and KDM5C Modulate Genome Activation and Stability in Porcine Embryos

Histone Lysine Demethylases KDM5B and KDM5C Modulate Genome Activation and Stability in Porcine Embryos

SPEN integrates transcriptional and epigenetic control of X-inactivation

Listening to mother: Long‐term maternal effects in mammalian development

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