Rbm46 Regulates Trophectoderm Differentiation by Stabilizing<i>Cdx2</i>mRNA in Early Mouse Embryos

Wang, Chenchen; Chen, Yuanfan; Deng, Hongkui; Gao, Shaorong; Li, Lingsong

doi:10.1089/scd.2014.0323

Cited by 8 publications

(6 citation statements)

References 38 publications

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“…As many of these proteins (70%) are still unknown to bind RNA, we also cannot exclude the presence of contaminant proteins that were non-specifically copurified with RBPs. Among the hESC-specific RBPs, we identified RBM46, which has been shown to bind the Cdx2 mRNA in mouse embryos (Wang et al, 2015) and whose precise levels are key determinants in controlling mESC differentiation (Zhai et al, 2017). This observation is consistent with the notion that some hESC-specific RBPs could represent general stem cell-related factors, irrespective of the species of origin.…”

Section: Resultssupporting

confidence: 85%

Uncovering the RNA-binding protein landscape in the pluripotency network of human embryonic stem cells

et al. 2021

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Embryonic stem cell (ESC) self-renewal and cell fate decisions are driven by a broad array of molecular signals. While transcriptional regulators have been extensively studied in human ESCs (hESCs), the extent to which RNA-binding proteins (RBPs) contribute to human pluripotency remains unclear. Here, we carry out a proteome-wide screen and identify 810 proteins that bind RNA in hESCs. We reveal that RBPs are preferentially expressed in hESCs and dynamically regulated during early stem cell differentiation. Notably, many RBPs are affected by knockdown of OCT4, a master regulator of pluripotency, several dozen of which are directly targeted by this factor. Using cross-linking and immunoprecipitation (CLIP-seq), we find that the pluripotency-associated STAT3 and OCT4 transcription factors interact with RNA in hESCs and confirm the binding of STAT3 to the conserved NORAD long-noncoding RNA. Our findings indicate that RBPs have a more widespread role in human pluripotency than previously appreciated.

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Section: Resultssupporting

confidence: 85%

Uncovering the RNA-binding protein landscape in the pluripotency network of human embryonic stem cells

et al. 2021

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“…For example, a recent study reported alterations in six metastable epialleles (CpG sequences with high inter-individual variation presumably due to stochastic methylation in early development) in 84 infants conceived during the protein-energy- and methyl-donor limited Gambian rainy season, in comparison to infants born in the dry season(57). Strikingly, one of the six nutrition-dependent epilalleles in the Gambian cohort(57), RBM46, encoding a regulator of early blastocyst and trophoectoderm differentiation(58), completely matched one of the G1 DMRs in our study (Gambia DMR hg18 , chr4:155,922,422-155,922,489, Barbados DMR: hg18, chr4: 155,921,670-155,922,589). Furthermore, DNA methylomics on 24 infants exposed to the war-related 1944/45 Dutch hunger winter at the time of conception, in comparison to their unaffected siblings, identified 181 DMRs, many of which related to growth and metabolism(59).…”

Section: Discussionsupporting

confidence: 53%

DNA Methylation Signatures of Early Childhood Malnutrition Associated With Impairments in Attention and Cognition

Peter

Fischer

Kundaković

et al. 2016

Biological Psychiatry

125

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Background Early childhood malnutrition affects 113 million children worldwide, impacting health and increasing vulnerability for cognitive and behavioral disorders later in life. Molecular signatures after childhood malnutrition, including the potential for intergenerational transmission, remain unexplored. Methods We surveyed blood DNA methylomes (~483,000 individual CpG sites) in 168 subjects across two generations (G1,G2), including 50 G1 individuals hospitalized during the first year of life for moderate to severe protein energy malnutrition, then followed up to 48 years in the Barbados Nutrition Study. Attention deficits and cognitive performance were evaluated with Connors Adult Attention Rating Scale (CAARS) and Wechsler Abbreviated Scale of Intelligence (WASI). Expression of nutrition-sensitive genes was explored by qRT-PCR in rat prefrontal cortex. Results We identified altogether 134 nutrition-sensitive differentially methylated genomic regions (DMR), with the overwhelming majority (87%) specific for G1. Multiple neuropsychiatric risk genes, including COMT, IFNG, MIR200B, SYNGAP1 and VIP2R showed associations of specific methyl-CpGs with attention and IQ. Interferon Gamma (IFNG) expression was decreased in prefrontal cortex of rats showing attention deficits after developmental malnutrition. Conclusions Early childhood malnutrition entails long lasting epigenetic signatures associated with liability for attention and cognition, and limited potential for intergenerational transmission.

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“…ESCs were grown on glass coverslips (Fisher Scientific) and stained as previously described ( Wang et al., 2015 ).…”

Section: Methodsmentioning

confidence: 99%

Phosphorylation of Threonine343 Is Crucial for OCT4 Interaction with SOX2 in the Maintenance of Mouse Embryonic Stem Cell Pluripotency

et al. 2017

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SummaryOCT4 is required to maintain the pluripotency of embryonic stem cells (ESCs); yet, overdose-expression of OCT4 induces ESC differentiation toward primitive endoderm. The molecular mechanism underlying this differentiation switch is not fully understood. Here, we found that substitution of threonine343 by alanine (T343A), but not aspartic acid (T343D), caused a significant loss of OCT4-phosphorylation signal in ESCs. Loss of such OCT4-phosphorylation compromises its interaction with SOX2 but promotes interaction with SOX17. We therefore propose that threonine343-based OCT4-phosphorylation is crucial for the maintenance of ESC pluripotency. This OCT4-phosphorylation-based mechanism may provide insight into the regulation of lineage specification during early embryonic development.

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Rbm46 Regulates Trophectoderm Differentiation by StabilizingCdx2mRNA in Early Mouse Embryos

Cited by 8 publications

References 38 publications

Uncovering the RNA-binding protein landscape in the pluripotency network of human embryonic stem cells

Uncovering the RNA-binding protein landscape in the pluripotency network of human embryonic stem cells

DNA Methylation Signatures of Early Childhood Malnutrition Associated With Impairments in Attention and Cognition

Phosphorylation of Threonine343 Is Crucial for OCT4 Interaction with SOX2 in the Maintenance of Mouse Embryonic Stem Cell Pluripotency

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