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Transcription Factors

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Abstract

Transcription factors are key controllers of gene expression. The activities of these proteins determine how a cell functions and responds to environmental perturbations. In humans there are approximately 3200 site-specific DNA binding transcription factors encoded by 1600 genes. The most characteristic domain of a transcription factor is its DBD, but the proteins also contain domains for homo- and heterodimerization and for contacts with co-factor proteins.

Only a small subset of the 3200 transcription factors are well understood, some of which belong to the nuclear receptors superfamily (Chap. 6). Many principles of transcriptional regulation in eukaryotes were identified first for nuclear receptors. One example is the dimerization of transcription factor DBDs that leads to a code for the specific recognition of the genomic binding sides. Bioinformatic methods substantially help to manage the understanding of sequence-specific recognition of genomic DNA by transcription factors. However, these methods only get efficient and reasonably accurate, when they are trained by genome-wide data, obtained, for example, by ChIP-seq approaches.

Transcription factors tend to be either rather ubiquitously expressed or are restricted to a specific tissue. They are either constitutively active or are regulated by an intra- or extra-cellular signal. Based on the mechanisms of their activation the latter transcription factors can be subdivided into at least four different classes.

In this chapter, we will provide the basis for the structural and functional understanding of site-specific transcription factors. This insight will be further extended for the link to signal transduction (Chap. 5) and the sensing of intra- and extra-cellular lipophilic molecules (Chap. 6).

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Additional Reading

  • Huang, P., Chandra, V., & Rastinejad, F. (2010). Structural overview of the nuclear receptor superfamily: insights into physiology and therapeutics. Annual Review of Physiology, 72, 247–272.

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  • Vaquerizas, J. M., Kummerfeld, S. K., Teichmann, S. A., & Luscombe, N. M. (2009). A census of human transcription factors: function, expression and evolution. Nature Reviews Genetics, 10, 252–263.

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  • Villar, D., Flicek, P., & Odom, D. T. (2014). Evolution of transcription factor binding in metazoans – mechanisms and functional implications. Nature Reviews Genetics, 15, 221–233.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Carlberg, C., Molnár, F. (2016). Transcription Factors. In: Mechanisms of Gene Regulation. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-7741-4_4

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