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Summary Lecture 3 - Transcriptional control of gene expression #2
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Lecture 3 - Transcriptional control of gene expression #2
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Biochemistry and Molecular Biology II – Lecture 3: Transcriptional control ofgene expression #2
23-04-2018
Eukaryotic gene regulation:
Operator = negative regulator
cAMP binds to CAP-site, causing higher levels of transcription
Eukaryotic gene control elements:
- Promoter proximal elements are ±100bp away from the core promoter.
Regulatory DNA elements in eukaryotes:
1. Core promoter elements: are situated close to (surrounding) the
transcriptional start site (-40 - +40bp) – the minimal sequence required for
transcriptional initiation.
e.g. TATA-box
2. Promoter proximal elements: upstream of the core promoter (-200 - -40bp) –
gene- or cell-type specific.
3. Enhancer/silencer: further than 200bp up- or downstream or even far away
from the protein coding gene – gene- or cell-type specific, orientation-
independent.
All three regulatory DNA elements are required for modulation of transcription.
Regulatory regions are diverse in eukaryotes:
CpG-islands: regulatory regions in eukaryotes;
- Lack core promoter elements but contain numerous CG dinucleotides.
- Regulates 60-70% of mammalian genes
- Transcription initiation is promiscuous and bidirectional
The core promoter and the pre-initiation complex:
Core promoter: consists out of the combination of distinct sequence motifs
e.g. TATA-box
Without the core promoter, there is no transcription.
The core promoter elements lie within -40 and +40 bp of the transcriptional start site
these elements all define the location of the transcriptional start site.
, Transcription initiation in eukaryotes:
- Formation of the pre-initiation complex (PIC) over the core promoter.
- General transcription factors:
e.g. TFIIA, TFIIB, TFIID (TBP + TAFs), TFIIE, TFIIF, TFIIH
all of the transcription factors contain ‘II’ in their sequence, because they work with
RNA polymerase II.
RNA polymerase II is involved in transcription initiation and elongation.
Activators and repressors can influence efficiency of PIC formation as well as
promoter clearance.
Transcription initiation:
In the presence of TATA-box:
1. The TATA-box is recognized by TBP (TATA-binding protein) and TAFs (TBP-
associated factors).
2. CpG-island’s promoter recruits TFIID via SP1 transcription factor.
In the absence of TATA-box:
1. Recruitment of TBP via protein-protein interactions (TFIID)
2. TAF subunits bind Inr and/or DPE elements
*There is a huge variety of transcription initiation complexes.
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