Learning the specific order of tf binding is not vital
Understand that transcription initiation involves MANY polypeptides,
each with a specific function.
Functions include: recognizing promoter sequences, modulating amount of transcript production, modulating time/space of transcript production, and unwinding DNA
Each tf/protein represents a functional unit
Transcription factors are denoted TFIIX, for Transcription Factor for polymerase II. X is an identifying letter.
Transcription initiation
Basal transcription factors - necessary for transcription
The first step in transcription initiation is TFIIA binds to the TATA box in the promoter region. The TATA box is the most strongly conserved consensus sequence in the eukaryotic promoter; it has the consensus sequence TATAAAA and is usually located around position -30 (counting backwards from the transcriptional start site). After TFIID binds to the TATA box, TFIIA joins the initiation complex, followed by TFIIB. Separate from the initiation complex, TFIIF binds to RNA polymerase II. One subunit of TFIIF has DNA-unwinding properties that presumably help RNA polymerase II unwind the DNA during transcription. Once the TFIIF-RNA polymerase complex has been formed, the two proteins can then join the initiation complex. After the addition of several more proteins to the initiation complex, transcripton is finally ready to begin.
Steps of transcription initiation - basal transcription factors
TFIID binds to the TATA box in the promoter region.
TFIIA joins initiation complex.
TFIIB joins initiation complex.
TFIIF binds RNA polymerase (separate from initiation complex).
RNA poly - THIIF complex binds initiation complex on DNA.
Regulatory transcription factors are non-intrinsic transcription factors that modulate the expression of a particular transcript. These are the transcription factors that regulate time/space differrential expression in the organism. These factors can be enhancers or silencers, meaning that they can both increase and decrease the expression of a given gene. Also, these transcription factors can act from several thousand base-pairs in either direction from the promoter. Here it is important to remember that the eukaryotic genome has significant secondary structure; DNA wrapping around nucleosomes and 30nm fiber looping can bring distant sequence motifs proximal to promoter sites where they can have significant action. It is important to remember that an enhancer/silencer sequence motif may be present without having an effect, because the specific transcription factor protein responsible for binding to that domain may not have been expressed, ie. may not be present. The sequence on its own has no effect, the presence of the modulatory transcription factor is required. This can complicate sequence analysis w/r/t expression because in some cases we will only have half of the contextual information (ie we are missing the protein context of the cell).
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Source:
OpenStax, Statistical machine learning for computational biology. OpenStax CNX. Oct 14, 2007 Download for free at http://cnx.org/content/col10455/1.2
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