Transcription factor

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

In molecular biology, a transcription factor is a protein that is important for the initiation of RNA polymerase during transcription . It can also be involved in the regulation of elongation and termination . Transcription factors can bind to the 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 take on various tasks and either bind directly to the DNA , for example to general motifs such as promoter elements ( e.g. the TATA box ), to the RNA polymerase or to other proteins of the pre-initiation complex .

These “basal” transcription factors always appear as complexes with other proteins. By binding to the DNA, they create a kind of "platform" for the RNA polymerase, the polymerase binds to the platform, and transcription is initiated. Transcription factors are diverse in their structure and have different tasks. Some have binding sites for important regulators (e.g. for antiterminators ), others have protein kinase functions or show helicase activity (e.g. TAF250-TFIID). They are ubiquitous; H. evenly present in all cells of an organism and usually have no part in specific gene regulation .

Specific transcription factors

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

Activators work on two principles:

  1. They bind the RNA polymerase complex. This gives the polymerase a higher binding affinity for the activated promoter, which means that it is now bound more strongly or the promoter strength is increased (at most one initiation per second), and the subsequent protein-coding sequence is expressed more intensely.
  2. They have or are recruiting histone acetyl transferase functions. The acetylation of histones loosens the chromatin , which gives the RNA polymerase better access to the DNA. It can therefore bind better to this and can therefore also be transcribed more efficiently.

Repressors work on the opposite principle, histone deacetylases lead to a more dense packaging of the DNA, and the blocking of polymerase binding sites leads to a lowering of the binding affinity. A complex regulation comes about through the network-like interaction of the many different transcription factors.

The activity of transcription factors is determined by their regulation.

Is 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)
  • Blockage of the DNA binding site (ligand on the bound TF prevents transcription)
  • Displacement from the DNA binding site (repressors prevent binding of activating TF)
  • Conditioning (order of interactions)

Types of transcription factors

Different types according to Jochen Graw:

Examples of specific transcription factors

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 u. a .: 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 evidence

  1. ^ JC Reese: Basal transcription factors . In: Current opinion in genetics & development (Curr. Opin. Genet. Dev.) . Volume 13, No. 2, April 2003, pp. 114-8. PMID 12672487 .
  2. ↑ Jochen Graw: Genetics. 4th edition, Springer, Berlin 2006, ISBN 978-3-540-24096-9 .