ArticleThe Journal of biological chemistry2019
The transcription factor TFCP2L1 induces expression of distinct target genes and promotes self-renewal of mouse and human embryonic stem cells.
Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 44 citations in OpenAlex.
- Systematic analysis of homozygous autosomal copy number losses in exomes improves diagnostic yield and uncovers ultra-rare recessive disorders.European journal of human genetics : EJHG · 2026Article
- The exit from naive pluripotency: a platform for the study of enhancer mechanistics.Biochemical Society transactions · 2025Review
- Tfcp2l1 as a central integrator of hypoxia, dedifferentiation, and tumor progression.Journal of experimental & clinical cancer research : CR · 2025Review
- TFCP2L1 drives stemness and enhances their resistance to Sorafenib treatment by modulating the NANOG/STAT3 pathway in hepatocellular carcinoma.Oncogenesis · 2024Article
- Hypoxia-induced immortalization of primary cells depends on Tfcp2L1 expression.Cell death & disease · 2024Article
- 3D Enhancer-promoter networks provide predictive features for gene expression and coregulation in early embryonic lineages.Nature structural & molecular biology · 2024Article
- Acoustic vibration promotes in vitro expansion of human embryonic stem cells.American journal of stem cells · 2024Article
- Systematic mapping and modeling of 3D enhancer-promoter interactions in early mouse embryonic lineages reveal regulatory principles that determine the levels and cell-type specificity of gene expression.bioRxiv : the preprint server for biology · 2023Article
- CXCR2 expression during melanoma tumorigenesis controls transcriptional programs that facilitate tumor growth.Molecular cancer · 2023Article
- Temporal and spatial staging of lung alveolar regeneration is determined by the grainyhead transcription factor Tfcp2l1.Cell reports · 2023Article
- Transcriptome-wide gene-gene interaction associations elucidate pathways and functional enrichment of complex traits.PLoS genetics · 2023Article
- A cellular hierarchy of Notch and Kras signaling controls cell fate specification in the developing mouse salivary gland.Developmental cell · 2023Article
- CELLoGeNe - An energy landscape framework for logical networks controlling cell decisions.iScience · 2022Article
- An integrated atlas of human placental development delineates essential regulators of trophoblast stem cells.Development (Cambridge, England) · 2022Article
- Host T Cell Dedifferentiation Effects Drive HIV-1 Latency Stability.Journal of virology · 2022Article
- Divergent roles for KLF4 and TFCP2L1 in naive ground state pluripotency and human primordial germ cell development.Stem cell research · 2021Article
- The chromatin accessibility landscape reveals distinct transcriptional regulation in the induction of human primordial germ cell-like cells from pluripotent stem cells.Stem cell reports · 2021Article
- ESRRB Facilitates the Conversion of Trophoblast-Like Stem Cells From Induced Pluripotent Stem Cells by Directly Regulating CDX2.Frontiers in cell and developmental biology · 2021Article
- Regulation of the expression of the estrogen related receptors (ERRs).Cellular and molecular life sciences : CMLS · 2020Review
- Putative Epigenetic Biomarkers of Stress in Red Blood Cells of Chickens Reared Across Different Biomes.Frontiers in genetics · 2020Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TFCP2L1 (transcription factor CP2-like 1) is a transcriptional regulator critical for maintaining mouse and human embryonic stem cell (ESC) pluripotency. However, the direct TFCP2L1 target genes are uncharacterized. Here, using gene overexpression, immunoblotting, quantitative real-time PCR, ChIP, and reporter gene assays, we show that TFCP2L1 primarily induces estrogen-related receptor β (Esrrb) expression that supports mouse ESC identity and also selectively enhances Kruppel-like factor 4 (Klf4) expression and thereby promotes human ESC self-renewal. Specifically, we found that in mouse ESCs, TFCP2L1 binds directly to the Esrrb gene promoter and regulates its transcription. Esrrb knockdown impaired Tfcp2l1's ability to induce interleukin 6 family cytokine (leukemia inhibitory factor)-independent ESC self-renewal and to reprogram epiblast stem cells to naïve pluripotency. Conversely, Esrrb overexpression blocked differentiation induced by Tfcp2l1 down-regulation. Moreover, we identified Klf4 as a direct TFCP2L1 target in human ESCs, bypassing the requirement for activin A and basic fibroblast growth factor in short-term human ESC self-renewal. Enforced Klf4 expression recapitulated the self-renewal-promoting effect of Tfcp2l1, whereas Klf4 knockdown eliminated these effects and caused loss of colony-forming capability. These findings indicate that TFCP2L1 functions differently in naïve and primed pluripotency, insights that may help elucidate the different states of pluripotency.
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