Endogenous epitope-tagging of Tet1, Tet2 and Tet3 identifies TET2 as a naïve pluripotency marker

Pantier, Raphaël; Tatar, Tülin; Colby, Douglas; Chambers, Ian

doi:10.26508/lsa.201900516

Cited by 17 publications

(20 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We reconstructed GRNs for 2iL and SL condition separately and compared the regulators as well as their specific targets ( Supplementary Figure S12 ; see ‘Materials and Methods’ section). We found several naïve pluripotency markers specifically enriched in 2iL condition including Nanog ( 56 ), Esrrb ( 57 ) and Tfcp2l1 ( 58 , 59 ), whereas heterogeneous and hypermethylated SL condition ( 60 , 61 ) regulators included Tet1 ( 62 , 63 ) and Dnmt3l ( 64 ) and Zfp57 ( 65 ) ( Supplementary Figure S12 ). Interestingly, Nme2 was a top mESC regulator for the 2iL GRNs.…”

Section: Resultsmentioning

confidence: 99%

TENET: gene network reconstruction using transfer entropy reveals key regulatory factors from single cell transcriptomic data

Kim

Jakobsen

Natarajan

et al. 2020

Nucleic Acids Research

View full text Add to dashboard Cite

Accurate prediction of gene regulatory rules is important towards understanding of cellular processes. Existing computational algorithms devised for bulk transcriptomics typically require a large number of time points to infer gene regulatory networks (GRNs), are applicable for a small number of genes and fail to detect potential causal relationships effectively. Here, we propose a novel approach ‘TENET’ to reconstruct GRNs from single cell RNA sequencing (scRNAseq) datasets. Employing transfer entropy (TE) to measure the amount of causal relationships between genes, TENET predicts large-scale gene regulatory cascades/relationships from scRNAseq data. TENET showed better performance than other GRN reconstructors, in identifying key regulators from public datasets. Specifically from scRNAseq, TENET identified key transcriptional factors in embryonic stem cells (ESCs) and during direct cardiomyocytes reprogramming, where other predictors failed. We further demonstrate that known target genes have significantly higher TE values, and TENET predicted higher TE genes were more influenced by the perturbation of their regulator. Using TENET, we identified and validated that Nme2 is a culture condition specific stem cell factor. These results indicate that TENET is uniquely capable of identifying key regulators from scRNAseq data.

show abstract

Section: Resultsmentioning

confidence: 99%

TENET: gene network reconstruction using transfer entropy reveals key regulatory factors from single cell transcriptomic data

Kim

Jakobsen

Natarajan

et al. 2020

Nucleic Acids Research

View full text Add to dashboard Cite

show abstract

“…This exciting possibility remains to be addressed. On the other hand, we and others have shown that TET1 and TET2 not only display specific patterns of expression in defined pluripotent subtypes (Fidalgo et al, 2016 ; Pantier et al, 2019 ; Mulholland et al, 2020b ), but most importantly, play opposite roles in regulating naïve and primed pluripotency (Fidalgo et al, 2016 ). While TET1 is important for primed pluripotency, TET2 is a key determinant of naïve one.…”

Section: An Expanded View Of Tet2 In Pluripotency In Vitro mentioning

confidence: 84%

The Complexity of TET2 Functions in Pluripotency and Development

Garcia-Outeiral

Parte

Fidalgo

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Ten-eleven translocation-2 (TET2) is a crucial driver of cell fate outcomes in a myriad of biological processes, including embryonic development and tissue homeostasis. TET2 catalyzes the demethylation of 5-methylcytosine on DNA, affecting transcriptional regulation. New exciting research has provided evidence for TET2 catalytic activity in post-transcriptional regulation through RNA hydroxymethylation. Here we review the current understanding of TET2 functions on both DNA and RNA, and the influence of these chemical modifications in normal development and pluripotency contexts, highlighting TET2 versatility in influencing genome regulation and cellular phenotypes.

show abstract

“…Interestingly, one of the NANOG-interaction domains (1522-1547) includes residues that interact with DNA, that lie adjacent to the TET1 catalytic domain and that are conserved in TET2 and TET3 [58]. We have recently identified two binding regions in TET2 that interact with NANOG and one of these includes residues homologous to TET1 1522-1547 [21]. Importantly, this region (1522-1547) also contains residues that bind methylated CpG [58].…”

Section: Tet1mentioning

confidence: 99%

“…TET protein activity is required both for proper differentiation [14,15] and reprogramming to pluripotency [16][17][18]. TET1 is the most highly expressed TET family protein both in pluripotent cells and during early development [19][20][21]. TET1 predominantly binds to promoters via its N-terminal CXXC domain which recognises unmethylated CpG dinucleotides [22][23][24][25].…”

Section: Introductionmentioning

confidence: 99%

TET1 interacts directly with NANOG via independent regions containing hydrophobic and aromatic residues

Pantier

Mullin

Hall-Ponsele

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

AbstractThe DNA demethylase TET1 is highly expressed in embryonic stem cells. Knockout experiments indicate that TET1 is important for lineage commitment, and paradoxically, also for reprogramming to naïve pluripotency. TET1 binds to promoters through a CXXC domain which recognises unmethylated CpG dinucleotides. TET1 also binds to enhancers, presumably via interactions with partner proteins. The transcription factor NANOG interacts with TET1 and is predominantly localised at enhancers in ESCs. Therefore, NANOG may contribute to TET1 biological activity in pluripotent cells. However, the regions of TET1 involved in protein-protein interactions are mostly unknown. Here, we characterise the physical interaction between TET1 and NANOG using embryonic stem cells and bacterial expression systems. TET1 and NANOG interact through multiple binding sites that act independently. Critically, mutating conserved hydrophobic and aromatic residues within TET1 and NANOG abolishes the interaction. Comparative ChIP-seq analysis identifies genomic loci bound by both TET1 and NANOG, that correspond predominantly to pluripotency enhancers. Importantly, around half of NANOG transcriptional target genes are associated with TET1-NANOG co-bound sites. These results indicate a mechanism by which TET1 protein is targeted to specific sites of action at enhancers by direct interaction with a transcription factor.HighlightsNANOG and TET1 have regulatory roles in maintaining and reprogramming pluripotencyTET1 and NANOG interact via multiple independent binding regionsTET1 and NANOG interactions are mediated by aromatic and hydrophobic residuesTET1 residues that bind NANOG are highly conserved in mammalsCo-localisation of TET1 and NANOG on chromatin is enriched at NANOG target genes

show abstract

Endogenous epitope-tagging of Tet1, Tet2 and Tet3 identifies TET2 as a naïve pluripotency marker

Cited by 17 publications

References 44 publications

TENET: gene network reconstruction using transfer entropy reveals key regulatory factors from single cell transcriptomic data

TENET: gene network reconstruction using transfer entropy reveals key regulatory factors from single cell transcriptomic data

The Complexity of TET2 Functions in Pluripotency and Development

TET1 interacts directly with NANOG via independent regions containing hydrophobic and aromatic residues

Contact Info

Product

Resources

About