Transcriptomic Regulation Driven by TCF12 Isoform Switching
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE307234 | GEO | 2025/11/11
REPOSITORIES: GEO
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Project description:Initial development of multicellular animals is controlled by maternal gene products stored in the oocyte. Homozygous mutations in the basic helix-loop-helix (bHLH) transcription factor TCF12 causes female infertile, but the impact of it on female reproduction is still unknown. Here, we prove evidence that TCF12 is abundantly expressed in the nucleus of growing oocytes at germinal vesicle (GV) stage, recognizing and binding target genes’ functional domain to moderate the transcriptional activity. Deletion of Tcf12 from oocytes of primordial follicles led to female sterility. Tcf12 though does not participate in meiotic maturation, unlike Tcf3 ablation, it is essential for fertilization and preimplantational development. On the one hand, Tcf12 maintains the competence of fertilization by controlling the proper expression and location of cortical granules and protease ovastacin (encoded by Astl). On the other hand, zygotes without TCF12 have a prolonged mitosis cell cycle upon a drop of protein phosphatase 2A (PP2A) activity inhibition, which further results in zygotic genome activation (ZGA) failure at the 2-cell stage. In the subsequent process of development, maternal knockout embryos gradually lose their development potential. Taken together, these observations clarified the maternal effect induced by Tcf12 ensures preimplantational development.
2023-11-07 | PXD046728 |
Project description:A Cartes d'Identite des Tumeurs (CIT) project from the french Ligue Nationale Contre le Cancer (http://cit.ligue-cancer.net: Anaplastic oligodendrogliomas (AOs) are rare primary brain tumors which are generally incurable with few treatment targets identified. Most oligodendrogliomas have chromosome 1p/19q co-deletion and IDH mutation. We analyzed 51 AOs by whole-exome and/or transcriptome sequencing identifying previously reported frequent somatic mutations in CIC and FUBP1 genes. We also identified recurrent mutations in TCF12 (11% of IDHmut-codel) which encodes basic helix-loop-helix (bHLFH) transcription factor 12 which is an oligodendrocyte-related transcription factor in IDHmut-codel tumors. Strikingly, the somatic mutations (encoding E548R and R602M substitutions) have not been reported previously in cancer but are identical to germline mutations causing craniosynostosis. Incorporating TCGA data on 43 AO tumors also implicates functional mutation of SMARCA4, NOTCH1, NOTCH2, SETD2, RBPJ and ARID1A/1B. These data are compatible with the combined deregulation of metabolism, chromatin organization/remodeling and Notch-pathway genes in AO oncogenesis. Our analysis provides further insights into the unique and shared pathways driving AO and new targets for therapeutic intervention.
2015-06-15 | E-MTAB-2767 | biostudies-arrayexpress
Project description:To investigate the regulation of TCF12 on downstream genes in OSCC, we performed GeneChip analysis using OECM1 expression cell subclones and HSC3 knockdown cell subclones.
2015-06-24 | GSE70186 | GEO
Project description:Stable ectopic TCF12 expression or knockdown in HCC cell lines was established by lentiviral infection. Then, MTT, colony formation, migration, invasion and HUVEC tube formation assays as well as an orthotopic xenograft model were used to investigate the biologic function of TCF12 in HCC cells in vitro and in vivo. Subsequently, RNA-Seq analysis was utilized to explore the target gene regulated by TCF12. RT-qPCR, western blotting, a dual-luciferase reporter assay, Ch-IP and functional rescue experiments were used to confirm the target gene regulated by TCF12. Finally, RT-qPCR, western blot and immunohistochemical (IHC) staining were performed to detect the expression level of TCF12 and to analyze the correlation of TCF12 with downstream genes as well as the clinical significance of TCF12 in human primary HCC.Our functional studies revealed that stable overexpression of TCF12 in human HCC cells enhanced cell proliferation, migration and invasion in vitro and in vivo, whereas knockdown of TCF12 showed opposing effects. Mechanistically, CXCR4 was a downstream target of TCF12, and TCF12 directly bound to the CXCR4 promoter to regulate its expression. Moreover, CXCR4, with its ligand CXCL12, played a critical role in tumor progression induced by TCF12 via activation of the MAPK/ERK and PI3K/AKT signaling pathways. Clinically, IHC analysis revealed that TCF12 was significantly associated with poor survival of HCC patients and that TCF12 expression was closely correlated with CXCR4 expression in primary HCC tissues. Our findings are the first to indicate that TCF12 could promote the tumorigenesis and progression of HCC mainly by upregulating CXCR4 expression and is a prognostic indicator for patients with HCC.
2019-09-23 | GSE133553 | GEO
Project description:Stable ectopic TCF12 expression or knockdown in HCC cell lines was established by lentiviral infection. Then, MTT, colony formation, migration, invasion and HUVEC tube formation assays as well as an orthotopic xenograft model were used to investigate the biologic function of TCF12 in HCC cells in vitro and in vivo. Subsequently, RNA-Seq analysis was utilized to explore the target gene regulated by TCF12. RT-qPCR, western blotting, a dual-luciferase reporter assay, Ch-IP and functional rescue experiments were used to confirm the target gene regulated by TCF12. Finally, RT-qPCR, western blot and immunohistochemical (IHC) staining were performed to detect the expression level of TCF12 and to analyze the correlation of TCF12 with downstream genes as well as the clinical significance of TCF12 in human primary HCC.Our functional studies revealed that stable overexpression of TCF12 in human HCC cells enhanced cell proliferation, migration and invasion in vitro and in vivo, whereas knockdown of TCF12 showed opposing effects. Mechanistically, CXCR4 was a downstream target of TCF12, and TCF12 directly bound to the CXCR4 promoter to regulate its expression. Moreover, CXCR4, with its ligand CXCL12, played a critical role in tumor progression induced by TCF12 via activation of the MAPK/ERK and PI3K/AKT signaling pathways. Clinically, IHC analysis revealed that TCF12 was significantly associated with poor survival of HCC patients and that TCF12 expression was closely correlated with CXCR4 expression in primary HCC tissues. Our findings are the first to indicate that TCF12 could promote the tumorigenesis and progression of HCC mainly by upregulating CXCR4 expression and is a prognostic indicator for patients with HCC.
2019-09-23 | GSE133675 | GEO
Project description:A Cartes d'Identite des Tumeurs (CIT) project from the french Ligue Nationale Contre le Cancer (http://cit.ligue-cancer.net); Anaplastic oligodendrogliomas (AOs) are rare primary brain tumors which are generally incurable with few treatment targets identified. Most oligodendrogliomas have chromosome 1p/19q co-deletion and IDH mutation. We analyzed 51 AOs by whole-exome and/or transcriptome sequencing identifying previously reported frequent somatic mutations in CIC and FUBP1 genes. We also identified recurrent mutations in TCF12 (11% of IDHmut-codel) which encodes basic helix-loop-helix (bHLFH) transcription factor 12 A Cartes d'Identite des Tumeurs (CIT) project from the french Ligue Nationale Contre le Cancer (http://cit.ligue-cancer.net); which is an oligodendrocyte-related transcription factor in IDHmut-codel tumors. Strikingly, the somatic mutations (encoding E548R and R602M substitutions) have not been reported previously in cancer but are identical to germline mutations causing craniosynostosis. Incorporating TCGA data on 43 AO tumors also implicates functional mutation of SMARCA4, NOTCH1, NOTCH2, SETD2, RBPJ and ARID1A/1B. These data are compatible with the combined deregulation of metabolism, chromatin organization/remodeling and Notch-pathway genes in AO oncogenesis. Our analysis provides further insights into the unique and shared pathways driving AO and new targets for therapeutic intervention.
2015-06-15 | E-MTAB-2771 | biostudies-arrayexpress
Project description:A Cartes d'Identite des Tumeurs (CIT) project from the french Ligue Nationale Contre le Cancer (http://cit.ligue-cancer.net); Anaplastic oligodendrogliomas (AOs) are rare primary brain tumors which are generally incurable with few treatment targets identified. Most oligodendrogliomas have chromosome 1p/19q co-deletion and IDH mutation. We analyzed 51 AOs by whole-exome and/or transcriptome sequencing identifying previously reported frequent somatic mutations in CIC and FUBP1 genes. We also identified recurrent mutations in TCF12 (11% of IDHmut-codel) which encodes basic helix-loop-helix (bHLFH) transcription factor 12 A Cartes d'Identite des Tumeurs (CIT) project from the french Ligue Nationale Contre le Cancer (http://cit.ligue-cancer.net); which is an oligodendrocyte-related transcription factor in IDHmut-codel tumors. Strikingly, the somatic mutations (encoding E548R and R602M substitutions) have not been reported previously in cancer but are identical to germline mutations causing craniosynostosis. Incorporating TCGA data on 43 AO tumors also implicates functional mutation of SMARCA4, NOTCH1, NOTCH2, SETD2, RBPJ and ARID1A/1B. These data are compatible with the combined deregulation of metabolism, chromatin organization/remodeling and Notch-pathway genes in AO oncogenesis. Our analysis provides further insights into the unique and shared pathways driving AO and new targets for therapeutic intervention.
2015-08-15 | E-MTAB-2772 | biostudies-arrayexpress
Project description:To investigate the regulation of TCF12 on downstream genes in OSCC, we performed GeneChip analysis using OECM1 expression cell subclones and HSC3 knockdown cell subclones. 4 samples
2015-06-24 | E-GEOD-70186 | biostudies-arrayexpress
Project description:The cascade of molecular events involved in mammalian sex determination has been shown to involve the SRY gene, but specific downstream events have eluded researchers for decades. The current study identifies one of the first direct downstream targets of the male sex-determining factor SRY as the basic-helix-loop-helix (bHLH) transcription factor TCF21. SRY was found to directly associate with the Tcf21 promoter SRY/SOX9 response element both in vitro and in vivo during male sex determination. TCF21 was found to promote an in vitro sex reversal of embryonic ovarian cells to promote precursor Sertoli cell differentiation. Therefore, SRY acts directly on the Tcf21 promoter to, in part, initiate a cascade of events associated with Sertoli cell differentiation and embryonic testis development. We used microarrays to determine genes whose expression was stimulated in rat E13 ovarian cell sub-cultures in the presence of a pCMV-myc-expression plasmid over-expressing the Sry, Tsf21, and/or Tcf12 (Reb-alfa) genes. RNA samples from the control group (untreated E13 rat ovarian cells) are compared to RNA from 4 groups of treated E13 rat ovarian cells: 1) Sry overexpressing, 2) Tcf21 overexpressing, 3) Tcf12 (Reb alfa) overexpressing, and 4) Tcf21 + Tcf12 (Reb-alfa) overexpressing. Untreated E13 testis cell sub-cultures were also analyzed. 3 biological replicates each group.
2011-04-25 | E-GEOD-24666 | biostudies-arrayexpress
Project description:Transcriptomic Regulation Driven by TCF12 Isoform Switching
| PRJNA1314802 | ENA