G9a co-localized with histone H3 lysine 9 monomethylation but not dimethylation in a nuclear membrane-dependent manner during mouse preimplantation embryo development

Li, Bo; Tang, Na; Chen, Shuqiang; Li, Xue; Xiang, Huang; Wang, Xiaohong; Sun, Fei

doi:10.1007/s10815-012-9911-y

Cited by 3 publications

(2 citation statements)

References 37 publications

(38 reference statements)

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“…What is more, G9a’s binding partner GLP also accumulates in 8C embryos ( Figure 1—figure supplement 1 ). These results, in line with a previous immunofluorescence study ( Li et al, 2013 ), indicate that even low levels of nuclear G9a at 4C stage are sufficient to initiate H3K9 dimethylation. Thus, following the burst of transcription at 2C stage, blastomeres accumulate substantial levels of repressive H3K9me2 mark, although its functional significance remains unclear.…”

Section: Resultssupporting

confidence: 92%

G9a regulates temporal preimplantation developmental program and lineage segregation in blastocyst

Ż̷ylicz

Borensztein

Wong

et al. 2018

eLife

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Early mouse development is regulated and accompanied by dynamic changes in chromatin modifications, including G9a-mediated histone H3 lysine 9 dimethylation (H3K9me2). Previously, we provided insights into its role in post-implantation development (Zylicz et al., 2015). Here we explore the impact of depleting the maternally inherited G9a in oocytes on development shortly after fertilisation. We show that G9a accumulates typically at 4 to 8 cell stage to promote timely repression of a subset of 4 cell stage-specific genes. Loss of maternal inheritance of G9a disrupts the gene regulatory network resulting in developmental delay and destabilisation of inner cell mass lineages by the late blastocyst stage. Our results indicate a vital role of this maternally inherited epigenetic regulator in creating conducive conditions for developmental progression and on cell fate choices.

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Section: Resultssupporting

confidence: 92%

G9a regulates temporal preimplantation developmental program and lineage segregation in blastocyst

Ż̷ylicz

Borensztein

Wong

et al. 2018

eLife

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“…The result of this combination is the acceleration of the process. Recently, G9a was found to colocalized with H3 lysine 9 monomethylation in a nuclear membrane-dependent manner during mouse embryo development [ 110 ]. Among the best characterized receptors that interact with the three regulatory elements of the OCT4 locus is the germ cell nuclear factor (GCNF).…”

Section: Conditions and Genes Governing Pre- And Post-implantation Emmentioning

confidence: 99%

Genes and Conditions Controlling Mammalian Pre- and Post-implantation Embryo Development

Anifandis¹,

Messini²,

Dafopoulos³

et al. 2015

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Embryo quality during the in vitro developmental period is of great clinical importance. Experimental genetic studies during this period have demonstrated the association between specific gene expression profiles and the production of healthy blastocysts. Although the quality of the oocyte may play a major role in embryo development, it has been well established that the post – fertilization period also has an important and crucial role in the determination of blastocyst quality. A variety of genes (such as OCT, SOX2, NANOG) and their related signaling pathways as well as transcription molecules (such as TGF-β, BMP) have been implicated in the pre- and post-implantation period. Furthermore, DNA methylation has been lately characterized as an epigenetic mark since it is one of the most important processes involved in the maintenance of genome stability. Physiological embryo development appears to depend upon the correct DNA methylation pattern. Due to the fact that soon after fertilization the zygote undergoes several morphogenetic and developmental events including activation of embryonic genome through the transition of the maternal genome, a diverse gene expression pattern may lead to clinically important conditions, such as apoptosis or the production of a chromosomically abnormal embryo. The present review focused on genes and their role during pre-implantation embryo development, giving emphasis on the various parameters that may alter gene expression or DNA methylation patterns. The pre-implantation embryos derived from in vitro culture systems (in vitro fertilization) and the possible effects on gene expression after the prolonged culture conditions are also discussed.

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G9a/RelB regulates self-renewal and function of colon-cancer-initiating cells by silencing Let-7b and activating the K-RAS/β-catenin pathway

et al. 2016

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Epigenetic reprogramming has been associated with the functional plasticity of cancer-initiating cells (CICs); however, the regulatory pathway has yet to be elucidated. A siRNA screen targeting known epigenetic genes revealed that G9a profoundly impairs the chemo-resistance, self-renewal and metastasis of CICs obtained from patients with colorectal cancer (CRC). Patients with elevated G9a were shown to face a high risk of relapse and poor survival rates. From a mechanistic perspective, G9a binds with and stabilizes RelB, thereby recruiting DNA methyltransferase 3 on the Let-7b promoter and repressing its expression. This leads to the activation of the K-RAS/β-catenin pathway and regulates self-renewal and function of CICs. These findings indicate that the G9a/RelB/Let-7b axis acts as a critical regulator in the maintenance of CIC phenotypes and is strongly associated with negative clinical outcomes. Thus, these findings may have diagnostic as well as therapeutic implications for the treatment of chemotherapy-resistant or metastatic CRC.

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G9a co-localized with histone H3 lysine 9 monomethylation but not dimethylation in a nuclear membrane-dependent manner during mouse preimplantation embryo development

Abstract: These results indicate dynamic changes in the expression level of H3K9m2 and G9a as preimplantation embryogenesis progresses. G9a co-localized with H3K9 m1 in a nuclear membrane-dependent manner during mouse preimplantation embryo development.

Cited by 3 publications

References 37 publications

G9a regulates temporal preimplantation developmental program and lineage segregation in blastocyst

G9a regulates temporal preimplantation developmental program and lineage segregation in blastocyst

Genes and Conditions Controlling Mammalian Pre- and Post-implantation Embryo Development

G9a/RelB regulates self-renewal and function of colon-cancer-initiating cells by silencing Let-7b and activating the K-RAS/β-catenin pathway

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