Activating Transcription. Activation of gene structure (Chromatin structure) Initiation and processing of transcription Transport to cytoplasm Translation of mRNA. transcription, splicing of mRNA, mRNA stability, translation efficiency,.
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Activation of gene structure(Chromatin structure)
Initiation and processing of transcription
Transport to cytoplasm
Translation of mRNA
splicing of mRNA,
Basal factors (TFs) and RNA polymerase bind to promoter and TATAA box.
Activators are proteins that recognize specific short DNA sequences inducing the efficiency of the promoters.
Co-activators are proteins required for a more efficient transcription. They do not bind DNA.
Regulators of chromatin structure
How do co-activators and regulators work in transcription?
---DNA-binding and Activating-binding domains are independent---(TF)
The two-hybrid system brings the idea of the co-activators
Activators may use a co-activator-two proteins-
Activators-one protein two domains
As long as protein complex binds both a specific DNA site and contacts the basal complex, the subunits can be encoded by separate genes.
How does the activator/co-activator stimulate transcription?
1- Induce some conformational change in the Transcriptional Complex
2-Increase the binding of the RNA polymerase to the promoter
3-Increase the efficiency of the Binding/Positioning of the RNA polymerase to the promoter
How does this increase in the efficiency of the Binding/Positioning of the RNA polymerase to the promoter stimulate transcription?
RNA polymerase exists as a holoenzyme (i.e. the enzyme is already associated with TFs)
Binding of the
TFs may manipulate the structure of chromatin
--affecting chromatin structure
--binding proteins to DNA sequence
---Expression of Histone 2B.
Testis tissues: Oct-1, CAAT
and TATA are associated
Embryonic tissues: another
proteins (repressors), not TFs,
are associated with CAAT boxes
are specific DNA sequences located in both promoter /enhancer regions,
which identify genes under common regulation
Metallothionein (MT) gene
TPA (phorbol esters)
Proteins bind to these specific regulatory elements.
General principle is that any one of several elements can independently activate the gene.
What does this general principle mean?
Modes of regulation vs.DNA-binding domain
Transcription factors are activated in different ways
Most regulatory schemes involve a modification of a protein that changes its conformation or location.
Activators may have the following domain/motifs:
-(Cys, His, Phe, Leu -Zn 2+ complex)
-Organized as a single tandem repeats
Steroid receptors(zinc finger) have several independent domains.Cys2/Cys2
Steroid receptors fall into two groups:
Glucocorticoid (GR), mineralocorticoid (MR), androgen (AR) and progesterone (PR) receptors all form homodimers that recognize the consensus sequence TGTTCT. The estrogen receptor (ER) is a homodimer that recognizes TGACCT.
Thyroid (T3R), vitamin D (VDR), retinoic acid (RAR) and 9-cis-retinoic acid (RXR) form heterodimers and recognize the sequence TGACCT. The other part of the heterodimer is RXR.
HLH proteins have a protein association domain and a DNA binding domain.
Dimerization and basic domains are necessary for DNA binding.
Leucine rich sequence
Activator Protein 1 (AP1), a transcription factor has two major subunits, Jun and Fos.