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Transcription factor

from Wikipedia, the free encyclopedia

DNA-binding domain of a glucocorticoid receptor from Rattus norvegicus with matching DNA fragment

In molecular biology, a transcription factor is a protein that is important for the initiation of RNA polymerase during transcription. It may also be involved in the regulation of elongation and termination. Transcription factors can bind to DNA and activate or repress the promoter. There are also transcription factors that do not bind directly to DNA but, for example, to other DNA-binding proteins. A distinction is made between general (basal) and gene-specific transcription factors.

General transcription factors

General transcription factors as subunits of the protein complexes required for transcription perform various tasks and bind either directly to DNA, for example to general motifs such as promoter elements (e.g. the TATA box), to RNA polymerase or to other proteins of the preinitiation complex.

These “basal” transcription factors always occur as complexes with other proteins. By binding to the DNA, they provide a kind of “platform” for the RNA polymerase, the polymerase binds to the platform, and transcription is initiated. Transcription factors are diverse in structure and have different roles. Some have binding sites for important regulators (e.g., antiterminators), others have protein kinase functions or exhibit helicase activity (e.g., TAF250-TFIID). They are ubiquitous, i.e. present uniformly in all cells of an organism, and usually have no part in specific gene regulation.[1]

Specific transcription factors

Specific transcription factors tell the polymerase which gene to transcribe. They are therefore only present in cells in which the gene they regulate is to be activated (or repressed, as the case may be). The DNA regions to which they bind have a specific sequence (so-called cis-elements such as enhancers or silencers) that is recognized and bound by the transcription factor. Specific transcription factors are usually activated by protein kinases. Activation is the end of a long signal transduction chain triggered by a receptor.

Activators work on two principles:

  1. They bind the RNA-polymerase complex. This gives the polymerase a higher binding affinity to the activated promoter, which is now bound more strongly, or the promoter strength is increased (maximum one initiation per second), and the subsequent protein-coding sequence is expressed more strongly.
  2. They have histone acetyl transferase function or recruit such. The acetylation of histones loosens the chromatin, giving RNA polymerase better access to the DNA. It can therefore bind to it better and thus be transcribed more efficiently.

Repressors work on a reverse principle, histone deacetylases lead to denser packaging of DNA, and blockade of polymerase binding sites is followed by lowering of binding affinity.
Complex regulation is achieved by the network-like interplay of the many different transcription factors.

The activity of transcription factors is determined by their regulation.

Regulated by

  • Binding of ligands (steroid hormones, estrogens, vitamins, thyroid hormones)
  • Phosphorylations (kinases, phosphatases)
  • Sumoylation
  • Acetylation
  • Maturation (domains of receptors anchored in the membrane)
  • Concentration (low concentrations activate, high ones inhibit the reaction)
  • DNA Binding
  • Binding of co-factors (binding of co-factors activates or inhibits transcription)
  • Formation of heterodimers (only complexes activate promoters)
  • Blockade of the DNA binding site (ligand on the bound TF prevents transcription)
  • Displacement from the DNA binding site (repressors prevent binding of activating TFs)
  • Conditioning (sequence of interactions)

Types of transcription factors

Different types according to Jochen Graw:[2]

  • Helix-turn-helix transcription factors
  • Homeodomain transcription factors
  • Helix-loop-helix transcription factors
  • Zinc finger transcription factors
  • Leucine zipper transcription factors

Examples of specific transcription factors

  • NF-AT
  • NF-κB
  • p53
  • STAT
  • CREB
  • CREB 2 (ATF-4)
  • Myogenin
  • Cdx proteins
  • Ap1
  • Estrogen receptors

Literature

  • Manfred Gossen, Jorg Kaufmann, Steven J. Triezenberg, S. Akira, Eric H. Asker, E. Assenat, B. Baumann, Don Lee Bohl, N. Corbi: Transcription factors. Springer, Berlin 2004, ISBN 3-540-21095-4.
  • Joseph Locker: Transcription factors. BIOS, Oxford 2001, ISBN 0-12-454345-6.
  • Gregg L. Semenza: Transcription factors and human disease. Oxford University Press, New York 1999, ISBN 0-19-511239-3.
  • Colin R. Lickwar, Florian Mueller et al: Genome-wide protein-DNA binding dynamics suggest a molecular clutch for transcription factor function. In: Nature. 484, 2012, pp. 251-255, doi:10.1038/nature10985

Individual references

  1. J. C. Reese: Basaltranscription factors. In: Current opinion in genetics & development (Curr. Opin. Genet. Dev.). vol. 13, no. 2, April 2003, pp. 114-8. PMID 12672487.
  2. Jochen Graw: Genetics. 4. Auflage, Springer, Berlin 2006, ISBN 978-3-540-24096-9.