Basal transcription of the human TBX3 gene, a key developmental regulator which is overexpressed in several cancers, requires functional NF-Y and Sp1 sites

Smith, James; Mowla, Shaheen; Prince, Sharon

doi:10.1016/j.gene.2011.07.013

Cited by 13 publications

(11 citation statements)

References 36 publications

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“…Other modules indicate novel functions for human NF-Y, such as, Golgi vesicle transport (#18), protein polymerization (#22), circadian rhythmic regulation (#24), cilium organization and spermatogenesis (#36), gland development (#53), platelet activation (#59), and cellular response to lipopolysaccharide (#38) (Table 1). Supporting our findings for novel modules #36 and #53, a NF-YB homolog in Schimidtea mediterranea is required for male germ cell development, while NF-Y binding sites are required for basal transcription of TBX3 , a key developmental regulator in module #53 27, 28 .…”

Section: Resultssupporting

confidence: 82%

Discovery of Novel Human Gene Regulatory Modules from Gene Co-expression and Promoter Motif Analysis

Snyder

Dinesh

2017

Sci Rep

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Deciphering gene regulatory networks requires identification of gene expression modules. We describe a novel bottom-up approach to identify gene modules regulated by cis-regulatory motifs from a human gene co-expression network. Target genes of a cis-regulatory motif were identified from the network via the motif’s enrichment or biased distribution towards transcription start sites in the promoters of co-expressed genes. A gene sub-network containing the target genes was extracted and used to derive gene modules. The analysis revealed known and novel gene modules regulated by the NF-Y motif. The binding of NF-Y proteins to these modules’ gene promoters were verified using ENCODE ChIP-Seq data. The analyses also identified 8,048 Sp1 motif target genes, interestingly many of which were not detected by ENCODE ChIP-Seq. These target genes assemble into house-keeping, tissues-specific developmental, and immune response modules. Integration of Sp1 modules with genomic and epigenomic data indicates epigenetic control of Sp1 targets’ expression in a cell/tissue specific manner. Finally, known and novel target genes and modules regulated by the YY1, RFX1, IRF1, and 34 other motifs were also identified. The study described here provides a valuable resource to understand transcriptional regulation of various human developmental, disease, or immunity pathways.

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Section: Resultssupporting

confidence: 82%

Discovery of Novel Human Gene Regulatory Modules from Gene Co-expression and Promoter Motif Analysis

Snyder

Dinesh

2017

Sci Rep

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“…TBX3 is overexpressed in several cancers, including pancreas, liver, breast cancer, and melanoma, 59 playing multiple roles in normal development and cancer. 60 In liver cancer, TBX3 was identified as a downstream target of the Wnt/β-catenin pathway, mediating β-catenin activities on cell proliferation and survival.…”

Section: Discussionmentioning

confidence: 99%

Identification of Genetic Susceptibility Loci for Colorectal Tumors in a Genome-Wide Meta-analysis

Peters¹,

Jiao²,

Schumacher³

et al. 2013

Gastroenterology

298

278

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BACKGROUND & AIMS Heritable factors contribute to the development of colorectal cancer. Identifying the genetic loci associated with colorectal tumor formation could elucidate the mechanisms of pathogenesis. METHODS We conducted a genome-wide association study that included 14 studies, 12,696 cases of colorectal tumors (11,870 cancer, 826 adenoma), and 15,113 controls of European descent. The 10 most statistically significant, previously unreported findings were followed up in 6 studies; these included 3056 colorectal tumor cases (2098 cancer, 958 adenoma) and 6658 controls of European and Asian descent. RESULTS Based on the combined analysis, we identified a locus that reached the conventional genome-wide significance level at less than 5.0 × 10−8: an intergenic region on chromosome 2q32.3, close to nucleic acid binding protein 1 (most significant single nucleotide polymorphism: rs11903757; odds ratio [OR], 1.15 per risk allele; P = 3.7 × 10−8). We also found evidence for 3 additional loci with P values less than 5.0 × 10−7: a locus within the laminin gamma 1 gene on chromosome 1q25.3 (rs10911251; OR, 1.10 per risk allele; P = 9.5 × 10−8), a locus within the cyclin D2 gene on chromosome 12p13.32 (rs3217810 per risk allele; OR, 0.84; P = 5.9 × 10−8), and a locus in the T-box 3 gene on chromosome 12q24.21 (rs59336; OR, 0.91 per risk allele; P = 3.7 × 10−7). CONCLUSIONS In a large genome-wide association study, we associated polymorphisms close to nucleic acid binding protein 1 (which encodes a DNA-binding protein involved in DNA repair) with colorectal tumor risk. We also provided evidence for an association between colorectal tumor risk and polymorphisms in laminin gamma 1 (this is the second gene in the laminin family to be associated with colorectal cancers), cyclin D2 (which encodes for cyclin D2), and T-box 3 (which encodes a T-box transcription factor and is a target of Wnt signaling to β-catenin). The roles of these genes and their products in cancer pathogenesis warrant further investigation.

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“…The antibodies used were as follows: guinea pig anti-human insulin, guinea pig anti-glucagon (both from Linco Research, St. Charles, MO), rabbit and goat anti-Pdx1 (a gift from Dr. Christopher Wright), rabbit anti-Tbx2 ( Bioworld Technology Inc, MN, USA), rabbit anti-Tbx3 (Invitrogen, CA, USA), goat anti-mouse carboxypeptidase A1 (R&D system, MN, USA), rat anti-E-cadherin (Sigma, St. Louis, MO), Fluorescin Dolichos Biflorus Agglutinin (Vector Laboratories, CA, USA), Alexa fluor donkey anti-rabbit (Molecular Probes Inc. Eugene, OR, USA), Texas redconjugated anti-guinea pig, Cy3 conjugated anti-rabbit, Cy3 conjugated anti-rat, and Cy3 conjugated anti-goat (all from Jackson Immuno Research, West Grove, PA). Western blot analysis of the Tbx2 and Tbx3 antibodies indicated that they each recognize as single band of the expected size (74 kDa and 79 kDa, respectively; Bioworld Technology, Inc. and Invitrogen product data sheets) (Smith et al, 2011). All sections were stained with 4', 6'-diamidine-2-phenylindole dihydrochloride (DAPI) for nuclear visualization.…”

Section: Methodsmentioning

confidence: 99%

Dynamic expression of Tbx2 and Tbx3 in developing mouse pancreas

Begum

Papaioannou

2011

Gene Expression Patterns

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Tbx2 and Tbx3 are closely related members of the T-box family of transcription factors that are important regulators during normal development as well as major contributors to human developmental syndromes when mutated. Although there is evidence for the involvement of Tbx2 and Tbx3 in pancreatic cancer, so far there are no reports characterizing the normal expression pattern of these genes in the pancreas. In this study, we examined spatial and temporal expression of Tbx2 and Tbx3 in mouse pancreas during development and in the adult using in situ hybridization and immunohistochemistry. Our results show that Tbx2 and Tbx3 are both expressed in the pancreatic mesenchyme throughout development beginning at embryonic day (E) 9.5. In addition, Tbx2 is expressed in pancreatic vasculature during development and in epithelial-derived endocrine and ductal cells during late fetal stages, postnatal development and in adult pancreas. In contrast, Tbx3 is expressed in exocrine tissue in the postnatal and adult pancreas. Further our results demonstrate that Tbx2 and Tbx3 are expressed in tumor-derived endocrine and exocrine cell lines, respectively. These dynamic changes in the expression pattern of these transcription factors lay the foundation for investigation of potential roles in pancreas development.

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Basal transcription of the human TBX3 gene, a key developmental regulator which is overexpressed in several cancers, requires functional NF-Y and Sp1 sites

Cited by 13 publications

References 36 publications

Discovery of Novel Human Gene Regulatory Modules from Gene Co-expression and Promoter Motif Analysis

Discovery of Novel Human Gene Regulatory Modules from Gene Co-expression and Promoter Motif Analysis

Identification of Genetic Susceptibility Loci for Colorectal Tumors in a Genome-Wide Meta-analysis

Dynamic expression of Tbx2 and Tbx3 in developing mouse pancreas

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