Transcription factors: Bridge between cell signaling and gene regulation

Transcription factors (TFs) are key regulators of intrinsic cellular processes, such as differentiation and development, and of the cellular response to external perturbation through signaling pathways. In this review we focus on the role of TFs as a link between signaling pathways and gene regulation. Cell signaling tends to result in the modulation of a set of TFs that then lead to changes in the cell's transcriptional program. We highlight the molecular layers at which TF activity can be measured and the associated technical and conceptual challenges. These layers include post-translational modifications (PTMs) of the TF, regulation of TF binding to DNA through chromatin accessibility and epigenetics, and expression of target genes. We highlight that a large number of TFs are understudied in both signaling and gene regulation studies, and that our knowledge about known TF targets has a strong literature bias. We argue that TFs serve as a perfect bridge between the fields of gene regulation and signaling, and that separating these fields hinders our understanding of cell functions. Multi-omics approaches that measure multiple dimensions of TF activity are ideally suited to study the interplay of cell signaling and gene regulation using TFs as the anchor to link the two fields.

Keywords: gene regulation; gene regulatory networks; literature bias; multiomics; postranslational modifications; signaling; transcription factors.

© 2021 The Authors. Proteomics published by Wiley-VCH GmbH.

Similar articles

Liu Q, Tan Y, Huang T, Ding G, Tu Z, Liu L, Li Y, Dai H, Xie L. Liu Q, et al. BMC Bioinformatics. 2010 Dec 14;11 Suppl 11(Suppl 11):S5. doi: 10.1186/1471-2105-11-S11-S5. BMC Bioinformatics. 2010. PMID: 21172055 Free PMC article.

Zhou Y, Ferguson J, Chang JT, Kluger Y. Zhou Y, et al. BMC Genomics. 2007 Oct 30;8:396. doi: 10.1186/1471-2164-8-396. BMC Genomics. 2007. PMID: 17971223 Free PMC article.

Ma X, Ezer D, Adryan B, Stevens TJ. Ma X, et al. Genome Biol. 2018 Oct 25;19(1):174. doi: 10.1186/s13059-018-1558-2. Genome Biol. 2018. PMID: 30359306 Free PMC article.

Brent MR. Brent MR. Trends Genet. 2016 Nov;32(11):736-750. doi: 10.1016/j.tig.2016.08.009. Epub 2016 Oct 6. Trends Genet. 2016. PMID: 27720190 Free PMC article. Review.

Jing Y, Lin R. Jing Y, et al. New Phytol. 2020 Aug;227(3):683-697. doi: 10.1111/nph.16602. Epub 2020 May 16. New Phytol. 2020. PMID: 32289880 Review.

Cited by

Otálora-Otálora BA, Payán-Gómez C, López-Rivera JJ, Pedroza-Aconcha NB, Aristizábal-Guzmán C, Isaza-Ruget MA, Álvarez-Moreno CA. Otálora-Otálora BA, et al. Front Cell Infect Microbiol. 2024 Aug 20;14:1425388. doi: 10.3389/fcimb.2024.1425388. eCollection 2024. Front Cell Infect Microbiol. 2024. PMID: 39228892 Free PMC article.

Wang S, Zhang B, Lou Z, Hu Y, Wang J, Wang J, Chen Z, Yin S. Wang S, et al. Heliyon. 2024 Jul 31;10(15):e35478. doi: 10.1016/j.heliyon.2024.e35478. eCollection 2024 Aug 15. Heliyon. 2024. PMID: 39170307 Free PMC article.

Lv J, Jiang C, Wu W, Mao K, Wei Q, Zheng Y, Gao C, Niu Z, Jin G, Zhang R, Mao J, Chen B, Ren G, Yang Y, Wan D. Lv J, et al. Hortic Res. 2024 Jun 21;11(8):uhae168. doi: 10.1093/hr/uhae168. eCollection 2024 Aug. Hortic Res. 2024. PMID: 39108575 Free PMC article.

Tang YC, Li R, Tang J, Zheng WJ, Jiang X. Tang YC, et al. BMC Bioinformatics. 2024 Jul 30;25(1):250. doi: 10.1186/s12859-024-05873-9. BMC Bioinformatics. 2024. PMID: 39080535 Free PMC article.

Wang J. Wang J. Biomolecules. 2024 Jun 24;14(7):749. doi: 10.3390/biom14070749. Biomolecules. 2024. PMID: 39062464 Free PMC article.

References

REFERENCES

    1. Spitz, F., & Furlong, E. E. M. (2012). Transcription factors: From enhancer binding to developmental control. Nature Reviews Genetics, 13, 613-626.
    1. Lambert, S. A., Jolma, A., Campitelli, L. F., Das, P. K., Yin, Y., Albu, M., Chen, X., Taipale, J., Hughes, T. R., & Weirauch, M. T. (2018). The human transcription factors. Cell, 172, 650-665.
    1. Takahashi, K., & Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 126, 663-676.
    1. Filtz, T. M., Vogel, W. K., & Leid, M. (2014). Regulation of transcription factor activity by interconnected post-translational modifications. Trends in Pharmacological Sciences, 35, 76-85.
    1. Karin, M., & Hunter, T. (1995). Transcriptional control by protein phosphorylation: Signal transmission from the cell surface to the nucleus. Current Biology, 5, 747-757.