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Hypothetical Model for Initiation of
Transcription
This simplified view of how
transcription is initiated at a particular gene,
presents a working hypothesis on how this may
occur.
1) A
promoter consisting
of a TATA-box homology and an uppstream regulatory
DNA sequence of a hypothetical gene is shown.
2) In the cell this DNA segment like all
other DNA is forming a chromatin fiber. A transcription
factor that has been activated into a DNA binding
state by a cellular signaling molecule, is searching
along the DNA and is able to find its
cognate gene
regulatory segment, where it binds sequence
specifically to the DNA.
3) This leads to the recruitment of
co-activator protein complexes to the
chromatin segment
that is able to open up the
chromatin
structure. One such class of factors is the so called
SWI/SNF complex. This complex, which is conserved
from yeast to man, is able to open up the nucleosome
structure during
hydrolysis of ATP
as the energy source. The other type of
chromatin opening
complex is the
histone acetyl
transferase (HAT) which is also conserved from yeast
to man.
4) The co-activators will effectuate a
chromatin opening,
which will also involve neighboring
promoter
structures.
5) This allows binding of basal
transcription factors such as the TATA-box binding
complex (which also was shown to contain HAT
activity) and other large co-activator complexes.
Each one of these various protein complexes contain
10-20 different polypeptides and a lot remains to be
learned about their mechanisms of action.
6) RNA polymerase binds either at this
stage or perhaps together with some other
co-activator complexes.
7) The
RNA polymerase
induces strand separation of the DNA and then starts
to copy the
coding strand of
DNA into an
RNA molecule.
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