Dynamic expression patterns of imprinted genes in human embryonic stem cells following prolonged passaging and differentiation

Mai, Xiuyun; Mai, Qingyun; Li, Tao; Zhou, Canquan

doi:10.1007/s10815-010-9524-2

Cited by 8 publications

(6 citation statements)

References 34 publications

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“…It has been reported that the expression level of H19 RNA increases during differentiation of mESCs8596061. Consistently, we observed that levels of H19 RNA increased during neural differentiation of mESCs by the SFEBq method on Day 5 and Day 7, while expression of a pluripotent gene, Oct4 , and a neural-progenitor-specific gene, Sox1 , are decreased and transiently increased, respectively (Fig.…”

Section: Resultssupporting

confidence: 89%

A G-quadruplex structure at the 5′ end of the H19 coding region regulates H19 transcription

Fukuhara

Toyoshima

2017

Sci Rep

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The H19 gene, one of the best known imprinted genes, encodes a long non-coding RNA that regulates cell proliferation and differentiation. H19 RNA is widely expressed in embryonic tissues, but its expression is restricted in only a few tissues after birth. However, regulation of H19 gene expression remains poorly understood outside the context of genomic imprinting. Here we identified evolutionarily conserved guanine (G)-rich repeated motifs at the 5′ end of the H19 coding region that are consistent with theoretically deduced G-quadruplex sequences. Circular dichroism spectroscopy and electrophoretic mobility shift assays with G-quadruplex-specific ligands revealed that the G-rich motif, located immediately downstream of the transcription start site (TSS), forms a G-quadruplex structure in vitro. By using a series of mutant forms of H19 harboring deletion or G-to-A substitutions, we found that the H19-G-quadruplex regulates H19 gene expression. We further showed that transcription factors Sp1 and E2F1 were associated with the H19-G-quadruplex to either suppress or promote the H19 transcription, respectively. Moreover, H19 expression during differentiation of mouse embryonic stem cells appears to be regulated by a genomic H19 G-quadruplex. These results demonstrate that the G-quadruplex structure immediately downstream of the TSS functions as a novel regulatory element for H19 gene expression.

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Section: Resultssupporting

confidence: 89%

A G-quadruplex structure at the 5′ end of the H19 coding region regulates H19 transcription

Fukuhara

Toyoshima

2017

Sci Rep

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“…In addition, our results also show that the expression level of IGF2 and H19 mRNA decreased during ESC isolation, from early to late passages of ESCs, in agreement with published human and mouse data (Sun et al, 2006;Humpherys et al, 2001;Rugg-Gunn et al, 2007;Mai et al, 2011;Sun et al, 2012). In contrast, the methylation rate of H19/IGF2 DMR remained stable from early to late passages, highlighting discordance between methylation status and expression levels of H19 and IGF2 during derivation of monkey ESC lines.…”

Section: Discussionsupporting

confidence: 91%

Epigenetic status of H19/IGF2 and SNRPN imprinted genes in aborted and successfully derived embryonic stem cell lines in non-human primates

et al. 2016

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The imprinted genes of primate embryonic stem cells (ESCs) often show altered DNA methylation. It is unknown whether these alterations emerge while deriving the ESCs. Here we studied the methylation patterns of two differentially methylated regions (DMRs), SNRPN and H19/IGF2 DMRs, during the derivation of monkey ESCs. We show that the SNRPN DMR is characteristically methylated at maternal alleles, whereas the H19/IGF2 DMR is globally highly methylated, with unusual methylation on the maternal alleles. These methylation patterns remain stable from the early stages of ESC derivation to late passages of monkey ESCs and following differentiation. Importantly, the methylation status of H19/IGF2 DMR and the expression levels of IGF2, H19, and DNMT3B mRNAs in early embryo-derived cells were correlated with their capacity to generate genuine ESC lines. Thus, we propose that these markers could be useful to predict the outcomes of establishing an ESC line in primates.

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“…For example, mouse and human Mkrn3 are expressed in differentiated cells derived from ESCs and are not expressed in proliferating ESCs (Jong et al, 1999a;Mai et al, 2011). In fibroblasts that transition out of the cell cycle, Mkrn1 is upregulated 6-fold; in several cancer cell lines that are induced to differentiate using retinoic acid, Mkrn1 is upregulated as well (Salvatico et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

“…Here, we report the discovery that another conserved protein, Makorin (Mkrn), regulates LIN-28 at the posttranslational level. Evidence accumulated from vertebrate systems (Abreu et al, 2013;Kim et al, 2005;Mai et al, 2011;Salvatico et al, 2010) points to roles for Mkrns in developmental processes that overlap with those regulated by LIN-28. Thus, the regulatory interaction between Mkrn and LIN-28 that we find in C. elegans might be of general significance in animal development.…”

Section: Introductionmentioning

confidence: 99%

LEP-2/Makorin regulates LIN-28 stability to promote the juvenile-to-adult transition in Caenorhabditis elegans

2016

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The heterochronic genes lin-28, let-7 and lin-41 regulate fundamental developmental transitions in animals, such as stemness versus differentiation and juvenile versus adult states. We identify a new heterochronic gene, lep-2, in Caenorhabditis elegans. Mutations in lep-2 cause a delay in the juvenile-to-adult transition, with adult males retaining pointed, juvenile tail tips, and displaying defective sexual behaviors. In both sexes, lep-2 mutants fail to cease molting or produce an adult cuticle. We find that LEP-2 post-translationally regulates LIN-28 by promoting LIN-28 protein degradation. lep-2 encodes the sole C. elegans ortholog of the Makorin (Mkrn) family of proteins. Like lin-28 and other heterochronic pathway members, vertebrate Mkrns are involved in developmental switches, including the timing of pubertal onset in humans. Based on shared roles, conservation and the interaction between lep-2 and lin-28 shown here, we propose that Mkrns, together with other heterochronic genes, constitute an evolutionarily ancient conserved module regulating switches in development.

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Dynamic expression patterns of imprinted genes in human embryonic stem cells following prolonged passaging and differentiation

Abstract: The global expression profiles of imprinted genes are generally stable in human embryonic stem cells after prolonged passaging and differentiation.

Cited by 8 publications

References 34 publications

A G-quadruplex structure at the 5′ end of the H19 coding region regulates H19 transcription

A G-quadruplex structure at the 5′ end of the H19 coding region regulates H19 transcription

Epigenetic status of H19/IGF2 and SNRPN imprinted genes in aborted and successfully derived embryonic stem cell lines in non-human primates

LEP-2/Makorin regulates LIN-28 stability to promote the juvenile-to-adult transition in Caenorhabditis elegans

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