Role of the bHLH transcription factor TCF21 in development and tumorigenesis

Abstract

Transcription factors control, coordinate, and separate the functions of distinct network modules spatially and temporally. In this review, we focus on the transcription factor 21 (TCF21) network, a highly conserved basic-helix-loop-helix (bHLH) protein that functions to integrate signals and modulate gene expression. We summarize the molecular and biological properties of TCF21 control with an emphasis on molecular and functional TCF21 interactions. We suggest that these interactions serve to modulate the development of different organs at the transcriptional level to maintain growth homeostasis and to influence cell fate. Importantly, TCF21 expression is epigenetically inactivated in different types of human cancers. The epigenetic modification or activation and/or loss of TCF21 expression results in an imbalance in TCF21 signaling, which may lead to tumor initiation and, most likely, to progression and tumor metastasis. This review focuses on research on the roles of TCF21 in development and tumorigenesis systematically considering the physiological and pathological function of TCF21. In addition, we focus on the main molecular bases of its different roles whose importance should be clarified in future research. For this review, PubMed databases and keywords such as TCF21, POD-1, capsulin, tumors, carcinomas, tumorigenesis, development, and mechanism of action were utilized. Articles were selected within a historical context as were a number of citations from journals with relevant impact.

High-resolution transcriptomic and epigenetic profiling identifies novel regulators of COPD phenotypes in human lung fibroblasts

“…Notably, the effects of TCF21 on proliferation and αSMA were stronger in diseased cells, indicating that COPD cells may be more sensitive to TCF21 loss that healthy lung fibroblasts. Consistent with the documented role of TCF21 in regulating cell proliferation in cancer (Lotfi et al 2021), its differential binding at strong enhancers in COPD fibroblasts could provide a molecular mechanism for the differential expression of DNA replication genes observed in our RNA-seq analysis.…”

Identification of key molecules and biological processes in TCF21 treated tumor pericytes

“…Transcription factor 21 (TCF21) is one of the basic helix-loop-helix (bHLH) transcription factors that control cell fate and differentiation that plays a critical role in a wide spectrum of biological processes, including organogenesis, proliferation, differentiation as well as invasion and metastasis of cancer cells 25 . Controlled expression and activity of TCF21 provide a changed transcriptional program that affects the progression of cancer 26 .…”

Role of Nuclear Non-Canonical Nucleic Acid Structures in Organismal Development and Adaptation to Stress Conditions

“…A second loop between the FLC promoter and termination site associates with FLC gene activity and this is lost as plants are transferred to cold (Crevillén et al, 2013). The transcription factor TCF21 plays a critical role in developing several cell types during embryogenesis (Lotfi et al, 2021). The expression of the TCF21 gene in human embryonic cells is controlled by an R-loop formed by the lncRNA TARID in the promoter of TCF21 gene (Figure 3).…”

“…The transcription factor TCF21 plays a critical role in developing several cell types during embryogenesis ( Lotfi et al, 2021 ). The expression of the TCF21 gene in human embryonic cells is controlled by an R-loop formed by the lncRNA TARID in the promoter of TCF21 gene ( Figure 3 ).…”