Chemistry of Life

Molecular genetics, biochemistry

transcription factors

Transcription factors are proteins that bind to DNA at specific promoter or enhancer or response element sequences or sites, at which they regulate transcription. As such they are required for the recognition of specific stimulatory sequences in eukaryotic and archaeal genes by RNA polymerases. Transcription factors can be selectively activated or deactivated by other proteins, often as the final step in signal transduction.

basal transcription apparatus : basal transcription factors : basal transcription initiation factors : consensus sequence : ELL : elongation : elongin : eukaryotic vs prokaryotic : general transcription factors : inducible transcription factors : initiation and preinitiation complex : preinitiation complex : P-TEFβ : regulatory transcription factors : specific transcription factors : TAFs : TATA binding protein : TATA-box : TBP : TFIIA, TFIIB, TFIID/TATA-box binding protein (TBP), TFIIE, TFIIF, TFIIH : TIIS : upstream transcription factors : upstream transcription factor functions

The basal transcription apparatus comprises RNA polymerase and that group of protein basal transciption factors that directly interact with it. The basal transcription apparatus is directly responsible for transcription. Three types of transcription factor are involved in transcription initiation: general transcription factors, upstream transcription factors, and inducible transcription factors.

General transcription factors (GTF's) are proteins that are important in the transcription of class II genes to mRNA templates.

Many GTFs are involved in the formation of a preinitiation complex, which, together with RNA polymerase II, bind to and read the single-stranded DNA gene template. Transcription inititation of all protein encoding genes in eukaryotes requires the formation of a preinitiation complex (PIC), which comprises RNA polymerase II and the basal transcription initiation factors: TFIIA, TFIIB, TFIID/TATA-box binding protein (TBP), TFIIE, TFIIF, and TFIIH.

TATA binding protein, (TBP) is a GTF that binds to the TATA-box, which is the motif of nucleic acids located directly upstream from the coding region in all genes. TBP directs recruitment of the RNA Pol II holoenzyme, the final event in transcription initiation. (When combined with an inactive apoenzyme, coenzymes form a complete, active enzyme called the holoenzyme.) These proteins are ubiquitous and interact with the core promoter region of DNA, which contains the transcription start site(s) of all class II genes. [] 3D image general transcription factor TBP - TATA binding protein [] 3D image transcription factor homeodomain - helix-turn-helix [] 3D transcription factor NFkappaB -helix-loop-helix []

The basal transcription factors are usually defined as that minimal complement of proteins necessary to reconstitute accurate transcription from a minimal promoter region (such as a TATA-box element or initiator sequence). As such, basal transcription factors are distinct from the regulatory transcription factors, which bind to sequences located farther from the initiation site, and which serve to modulate levels of transcription.

Some GTFs participate in the elongation phase of transcription. For example, members of the FACT complex, Spt16/Pob3, facilitate the rapid movement of RNA Pol II over the encoding region of genes. This is accomplished by removing the histone octamer from the path of an active polymerase and thereby decondensing the heterochromatin.

Upstream transcription factors (or upstream binding factors) are proteins that bind to a cis-regulatory element (such as an enhancer or repressor sequence) upstream from a gene. Upstream transcription factors are ubiquitous factors that increase the efficiency of transcription initiation because they directly or indirectly affect the initiation of transcription. A set of upstream factors is unique to each promoter.

Upstream factors function to:
● influence transcription initiation by interacting with members of the basal apparatus
● most interactions are positive and induce transcription
● promote assembly of the apparatus
● can bind coactivators that interact with the basal apparatus
repressors can prevent assembly of the basal apparatus
● typically bind to TFIID, TFIIB, or TFIIA
TFIID/TATA-box binding protein provides various TATA-binding protein-associated factors (TAFs), which can interacted with upstream factors. For TAFs that are unique to a specific promoter, interaction with upstream factors can control promoter-specific transcription.
Inducible transcription factors act similarly to upstream transcription factors, but they require activation or inhibition. Inducible factors act in the same manner as do upstream factors, but they are regulated in a temporal or spatial manner, or respond directly to the environment.

Eubacterial : none.
Archaeal : TBP, TFIIB, and TIIS homologs of eukaryal RNA polymerase II-associated factors described thus far.
Eukaryotic : TBP, TAFs, TFIIA, TFIIB, TFIIE, TFIIF, TFIIH required for RNA polymerase II initiation; P-TEFβ, TFIIS, TFIIF, elongin, and ELL required for elongation.

Table  Comparisons of Eubacteria, Archaea, and Eukaryotes :
Table Candidate proteins linking transcription and pre-mRNA splicing :

A consensus sequence may be a short sequence of nucleotides that is found several times in the genome and is thought to play the same role in its different locations. Many transcription factors recognise particular consensus sequences in the promoters of the genes that they regulate.

Specific transcription factors:
regulatory § NF-κB

Evolving intricacies and implications of E2F1 regulation.
E2F transcription factors may play a pivotal role in the transcriptional regulation of several cellular processes far beyond the originally described cell cycle and proliferation. Among the six E2F family members, only E2F1 is noted for its role in apoptosis. The pocket protein family members Rb, p107, and p130 act as the main regulators of E2F activity. Nonetheless, in recent years other protein-protein interactions have been described for E2Fs. The post-translational modifications resulting from such protein interactions may have significant implications in the stability, half-life, and functional activity of E2Fs. In human diseases the significance of E2Fs is still under appreciated and is primarily recognized only as a consequence of the impairment in retinoblastoma gene product (Rb). However, with increasing knowledge of other protein interactions, the derailment of E2F activity could be anticipated to stem from an abnormality of any node in the complex network governing their availability and activity. The present review is intended to provide a perspective on the diversity of biochemical mechanisms underlying abnormal E2F expression and activity, understanding of which may have significant clinical implications. Mundle SD, Saberwal G. Evolving intricacies and implications of E2F1 regulation. (Free Full Text Article) FASEB J. 2003 Apr;17(6):569-74.

Distinct recruitment of E2F family members to specific E2F-binding sites mediates activation and repression of the E2F1 promoter. [Oncogene. 2003] PMID: 14576826
Regulation of endogenous E2F1 stability by the retinoblastoma family proteins. [Proc Natl Acad Sci U S A. 1999] PMID: 10077601
Unique roles for E2F1 in the mouse lens in the absence of functional pRB proteins. [Invest Ophthalmol Vis Sci. 2002] PMID: 11980867
E2Fs regulate the expression of genes involved in differentiation, development, proliferation, and apoptosis. [Genes Dev. 2001] PMID: 11159908
Regulation of E2F: a family of transcription factors involved in proliferation control. [Gene. 1999] PMID: 10521653
See all Related Articles...

3-D Structure Of Human Transcription Factor Proteins Revealed:
A combination of electron microscopy and single particle image analysis has been used to produce the first three-dimensional images of the protein complex that initiates the transcription of DNA's genetic code for the subsequent production of new proteins. 3D image TFIID

Transcription Factor Protein's Role In Cell Death, Neurodegeneration And Schizophrenia:
Researchers at the University of Pennsylvania School of Medicine discovered that a protein called Elk-1 interacts with mitochondria, the energy storehouse of a cell, suggesting that this protein – typically active in the nucleus – could play a role in cell death and mitochondria-related diseases such as neurodegeneration and schizophrenia.



Anonymous Anonymous said...

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1:23 PM  
Anonymous Anonymous said...

In general, a consensus sequence is that idealized sequence in which each position represents the base/amino acid most often found when many sequences are compared. A genetic consensus sequence is a sequence of nucleotides that is common to different genes or genomes. There may be some variations but such sequences show considerable similarity. So, a consensus sequence is the prototype sequence that most others approach.

These are evolutionarily conserved motifs that are disclosed by multiple sequence alignments when species are compared by software algorithms for pattern recognition. Such bioinformatic analyses reveal which sequences are conserved (unchanged) over evolutionary time. Such conserved sequences are often regulatory sequences that control biosynthesis or they are signal sequences that regulate maturation or direct molecules to specific intracellular sites. Evolutionary distance can be estimated by the amount of divergence of variable residues and evolutionary relatedness by the conservation of such sites.

A gene class can be defined as a group of genes with related functions, or by biologically relevant information. For example, a class could be defined by a signal transduction or metabolic pathway, by the members of a protein complex, or by an enzymatic activity. So, a gene can be a member of any number of classes, and hundreds if not thousands of gene classes can be defined on the basis of function.

Class II genes code for proteins and are transcribed by RNAp II. The promoter region of Class II genes often contains a TATA box, and thei basal transcription requires formation of a preinitiation complex.

1:29 PM  

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