Multiple biological functions of transcription factor 21 in the development of various cancers

Jiang, Xiaodi; Yang, Zhi

doi:10.2147/ott.s164033

Cited by 18 publications

(15 citation statements)

References 68 publications

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“…For instance, the mapped loci showing co-localization of AP-1 and TCF21 are enriched for genes that contribute to VEGF , TGFβ , EGF , Hippo, focal adhesion, and cell cycle biological processes (Additional file 1: Figure S4H). These terms are well known to associate with various forms of cancer, and the data presented here are consistent with both the involvement of AP-1 and TCF21 interactions in the biology of the tumor cell, since TCF21 is a well-known tumor suppressor [59], as well as the angiogenic processes that support tumor growth and expansion [60, 61].…”

Section: Discussionsupporting

confidence: 82%

TCF21 and AP-1 interact through epigenetic modifications to regulate coronary artery disease gene expression

et al. 2019

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Background Genome-wide association studies have identified over 160 loci that are associated with coronary artery disease. As with other complex human diseases, risk in coronary disease loci is determined primarily by altered expression of the causal gene, due to variation in binding of transcription factors and chromatin-modifying proteins that directly regulate the transcriptional apparatus. We have previously identified a coronary disease network downstream of the disease-associated transcription factor TCF21 , and in work reported here extends these studies to investigate the mechanisms by which it interacts with the AP-1 transcription complex to regulate local epigenetic effects in these downstream coronary disease loci. Methods Genomic studies, including chromatin immunoprecipitation sequencing, RNA sequencing, and protein-protein interaction studies, were performed in human coronary artery smooth muscle cells. Results We show here that TCF21 and JUN regulate expression of two presumptive causal coronary disease genes, SMAD3 and CDKN2B-AS1 , in part by interactions with histone deacetylases and acetyltransferases. Genome-wide TCF21 and JUN binding is jointly localized and particularly enriched in coronary disease loci where they broadly modulate H3K27Ac and chromatin state changes linked to disease-related processes in vascular cells. Heterozygosity at coronary disease causal variation, or genome editing of these variants, is associated with decreased binding of both JUN and TCF21 and loss of expression in cis , supporting a transcriptional mechanism for disease risk. Conclusions These data show that the known chromatin remodeling and pioneer functions of AP-1 are a pervasive aspect of epigenetic control of transcription, and thus, the risk in coronary disease-associated loci, and that interaction of AP-1 with TCF21 to control epigenetic features, contributes to the genetic risk in loci where they co-localize. Electronic supplementary material The online version of this article (10.1186/s13073-019-0635-9) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 82%

TCF21 and AP-1 interact through epigenetic modifications to regulate coronary artery disease gene expression

et al. 2019

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“…The helix-loop-helix (HLH) family of transcription factors possesses highly conserved bipartite domains for DNA binding and protein-protein interactions, which is pivotal in various developmental processes, covering myogenesis, neurogenesis, and hematopoiesis (Jiang and Yang, 2018). The HLH family members are divided into seven families according to tissue distribution, dimerization ability, and DNA binding specificity (Massari and Murre, 2000).…”

Section: Introductionmentioning

confidence: 99%

“…The HLH family members are divided into seven families according to tissue distribution, dimerization ability, and DNA binding specificity (Massari and Murre, 2000). Transcription factor 21 (TCF21, 6417bp)-also known as Pod1, bHLHa23, or Capsulin-encodes a transcription factor belonging to the cell-type-specific class II basic helix-loop-helix (bHLH) family at chromosome 6q23.2 (Jiang and Yang, 2018). Moreover, TCF21 is specific for mesoderm and is expressed in the embryos' mesenchymal derived tissues, such as the epicardium, lung, intestine, gonad, and kidney (Plotkin and Mudunuri, 2008).…”

Section: Introductionmentioning

confidence: 99%

The Role of Transcription Factor 21 in Epicardial Cell Differentiation and the Development of Coronary Heart Disease

Shen

Wang

et al. 2020

Front. Cell Dev. Biol.

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Transcription factor 21 (TCF21) is specific for mesoderm and is expressed in the embryos' mesenchymal derived tissues, such as the epicardium. It plays a vital role in regulating cell differentiation and cell fate specificity through epithelial-mesenchymal transformation during cardiac development. For instance, TCF21 could promote cardiac fibroblast development and inhibit vascular smooth muscle cells (VSMCs) differentiation of epicardial cells. Recent large-scale genome-wide association studies have identified a mass of loci associated with coronary heart disease (CHD). There is mounting evidence that TCF21 polymorphism might confer genetic susceptibility to CHD. However, the molecular mechanisms of TCF21 in heart development and CHD remain fundamentally problematic. In this review, we are committed to providing a detailed introduction of the biological roles of TCF21 in epicardial fate determination and the development of CHD.

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“…The activation of TCF21 by long ncRNA TCF21 antisense RNA-inducing demethylation (TARID) by induction of promoter demethylation. Promoter of TCF21 in third CpG guides the TARID transcription, thereby inducing the DNA demethylation (TET protein-dependent) resulting TCF21 transcriptional activation and interaction of TARID to promoter of TCF21 , which inducts GADD45A/TDG to base excision repair (BER) for demethylation processes 29 . A recent study on TCF21 revealed the expression of TCF21 in normal lung airways with the observation of aberrantly methylated and silenced in majority of non-small lung carcinomas 30 .…”

Section: Resultsmentioning

confidence: 99%

Genetic evaluation of the variants using MassARRAY in non-small cell lung cancer among North Indians

Bhat

Sethi

Bhat

et al. 2021

Sci Rep

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Lung cancer is genetically diverse and a major health burden. Non-small cell lung cancer (NSCLC) accounts for 80% of total lung cancer cases and 20% cases are Small cell lung cancer (SCLC). The present case–control association study focused on the cost effective high throughput genotyping using Agena MassARRAY matrix-assisted laser desorption/ionization-time of flight, mass spectrometry (MALDI-TOF) platform to analyze the genetic association of candidate genetic variants. We performed multiplex PCR and genotyped twelve single nucleotide polymorphisms (SNPs) in 723 samples (162 NSCLC cases and 592 healthy controls). These genetic variants were selected from literature for their association with various cancers worldwide and this is the first study from the region to examine these critically important genetic variants. With prospective case–control association study design, twelve variants from ten genes were evaluated. Amongst these six variants, TCF21 (rs12190287), ERCC1 (rs2298881, 11615), ERCC5 (rs751402), ARNTL (rs4757151), BRIP1 (rs4986764) showed significant association with NSCLC risk (p ≤ 0.003) in Jammu and Kashmir population. In-silico findings of these genetic variants showed remarkable functional roles that needs in-vitro validations. It is further anticipated that such case control studies will help us in understanding the missing heritability of non-small cell lung cancer.

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Multiple biological functions of transcription factor 21 in the development of various cancers

Cited by 18 publications

References 68 publications

TCF21 and AP-1 interact through epigenetic modifications to regulate coronary artery disease gene expression

TCF21 and AP-1 interact through epigenetic modifications to regulate coronary artery disease gene expression

The Role of Transcription Factor 21 in Epicardial Cell Differentiation and the Development of Coronary Heart Disease

Genetic evaluation of the variants using MassARRAY in non-small cell lung cancer among North Indians

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