Transcription factor

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Transcription factors are proteins that bind to specific DNA sequences in order to regulate gene expression. They can act as activators or repressors, respectively increasing or decreasing the transcription of a target gene. Some transcription factors function by directly recruiting (or, conversely, blocking the recruitment of) RNA polymerase to the promoter region of a target gene; however, the majority of transcription factors function through interaction with one or more adapter proteins.[1]

Transcription factors comprise several protein families (groups of closely related proteins), many of which are found in every lineage of organism. Genes encoding for transcription factors make up a significant portion of every organism's genome. There are estimated to be well over 2000 genes (some estimates are as high as 3000) encoding for transcription factors in the human genome (~10% of all human genes)[2][3]. These genes tend to be highly conserved and, in many instances, can be functionally interchangeable between organisms of different clades.

Contents

Structure

Like all proteins, transcription factors are composed of discrete functional modules called "domains". Transcription factors generally contain at least two functional domains, a DNA binding domain (DBD) and a trans-activating domain (TAD). Some transcription factors also possess a signal sensing domain (SSD).

The DNA binding domain is the domain that recognizes and binds to a specific DNA sequence. DNA sequences recognized by the DNA binding domains of transcription factors are often called enhancer sequences (often shortened simply to "enhancers"). They can also be called DNA binding sites or (in the case of sequences recognized by nuclear hormone receptors) response elements. Depending on the transcription factor, these sequences can be as short as 4 base pairs or as long as 30 base pairs (in a few rare instances, they can be even longer).

The trans-activating domain is the part of the transcription factor that interacts with and binds to other proteins.

In transcription factors with a signal sensing domain, the signal sensing domain is the part of the trascription factor that binds to chemical signals (e.g. a steroid hormone or cAMP), allowing the transcription factor to function in response to a particular chemical signal.

Function

Transcription factors work by recruiting RNA polymerase to the promoter region of a gene, or by blocking the access of RNA polymerase to a promoter. This can be accomplished by direct interaction with the RNA polymerase, indirect interaction with the RNA polymerase via adapter proteins, or through interaction with histone-modifying enzymes.

As major regulators of gene expression, transcription factors play a role in all cell processes. Depending on the transcription factor, this can range from regulation of cell metabolism to regulation of cell cycle. In complex organisms, specific transcription factors regulate developmental processes and cell differentiation.

The mechanism through which a transcription factor functions, and its regulatory effect (up-regulation or down-regulation) on a target gene, varies widely between transcription factors. The regulatory effect (and sometimes mechanism) of a specific transcription factor often varies depending on the target gene, and can sometimes even vary in response to other factors within the cell.

See Also

Gene regulation

Gene expression

Molecular biology

Developmental biology

Transcription

Central dogma of molecular biology

References

  1. Weaver, Robert F. Molecular Biology. 4th ed. Boston: McGraw-Hill, 2008.
  2. http://www.ncbi.nlm.nih.gov/pubmed/11823631
  3. http://www.ncbi.nlm.nih.gov/pubmed/15193307
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