Lecture notes

Lecture notes BIOL3015 Transcriptional control and genetic diseases

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University Of Southampton (UOS)

Lecture notes from BIOL3015 regulation of gene expression, transcriptional control and genetic diseases. Covering: transcriptional control, TATA box, TATA-less promotors, MyoD gene, activation domains, transcriptional factors

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Uploaded on December 11, 2023
Number of pages 6
Written in 2021/2022
Type Lecture notes
Professor(s) Karen lillycrop
Contains Biol3015 transcriptional control and genetic diseases

transcriptional control
genetic disease
genes
regulation
transcription
tata
promotors
mediators
enhancers
silencers
insulators
regulation of gene expression

Institution University of Southampton (UOS)
Education Unknown
Module Unknown

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Transcriptional control and genetic diseases
Transcriptional control
The complexity of the eukaryotic system
 RNA Polymerase I transcribes ribosomal RNA genes
 RNA Polymerase II transcribes Protein coding genes miRNAs – non coding RNAs
 RNA polymerase III transcribes tRNA genes
Core promotor
 Transcriptions starts at +1 shown by an arrow
 Downstream is positive, upstream is negative
Inr (initiator elements)
 Transcription usually starts at an A flanked by pyrimidine rich sequence
 This region is called the initiator
 YY A NYAYY
 YY – pyramidine
 A start base

The TATA box
 Sequence RNApol
 Transcription about 30 bases downstream
 The conserved C-terminal domain of TBP binds to TATA-box DNA
 TATA-binding protein = TBP
Stepwise assembly of Pol II transcription-initiation complex
TFIID
 Binds first
 Binds to TATA
 800KD in size
 TBP – TATA box binder – recognises box – 30KD
 When binding DNA bends at 90o angle
 TAFs – 11 of them – 18-250 KD – associated factors
TFIIA
 Binds next
 Stabalises reaction of TFIID with DNA
TFIIB
 Binds next
 Binds solo through protein interactions
 Recruits RNApol to DNA
RNApol II
 Comes with TFIIF
TFIIE
 ATPase – provides energy
TFIIH
 Helicase

A pre-initiation complex (PIC) is assembled
 DNA strands split
 Initiation of transcription

, TATA less promoters
 Only 25% of genes have TATA box
 Other 75% have an INR and DPE
DPE
 DPE is a downstream promoter element
 DPE have the sequence AGAC
 Located +28 and +32
TFII I recognises DPE – transcription starts

Genes with TATA box
 Single start site
 Highly controlled genes
DPE genes
 Multiple start sites
 Constitutively expressed genes

Transcription initiation at eukaryotic protein-coding genes
# of subunits Activity
RNA pol II 12 RNA synthesis
General TX factors
TFIID 9 Promoter recognition
TFIIB 1
TFIIE 2
TFIIF 2
TFIIH 9 Helicase

Upstream Sequence Elements (USEs)
 MyoD – activates gene in muscle cells – binds to GGGCGG
 PIC directs only a low level of transcription
 Transcription is enhanced by the binding of transcription factors to sites upstream,
of the TATA/Inr
Transcription factors that confer general transcription
 SP1
 GGGCGG
Transcription factors that confer tissue specific transcription
 MyoD – CANNTG - Muscle Specific
 Oct-2 – ATGCAAT - B cell specific
Transcription factors that confer inducible transcription
 CREB - T/GT/ACGTCA - cAMP
 Estrogen receptor – AGGTCANNNTGACCT - Estrogen
Regulatory sequences that act at a distance
1. Enhancers
2. Silencers
3. Insulators
4. LCRs

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