Regulation Of Gene Expression Flashcards
Prokaryotic expression regulation
- Regulatory molecules = transcription factors
* repressors
* activators - Promoter = RNA transcriptionase binds (one for several genes)
- Operons
* inducible: usually off, can be induced
* repressible: usually on, can be repressed
Lac Operon
In E. Coli
- inducible
1. Glucose only = off- no cAMP => CAP unbound
- lac 1 (repressor gene) active
- repressor protein occupies operator => no transcription
- no mRNA => no protein
2. Lactose only = on - adenylyl Cyclase active -> cAMP
- cAMP binds CAP -> CAP binding site
- allolactose binds represser => RNA polymerase can bind strand
- mRNA made -> proteins
3. Lactose + glucose = off - adenylyl cyclase inhibited => no cAMP
- no CAP/cAMP complex => no transcription
Eukaryotic Expression regulation
- Transcriptional
- Post-transcriptional
- Translational
- Post-translational
- Epigenetic
Eukaryotic transcriptional regulation
- Regulation molecules
A. Cis-acting elements- part of DNA
*core promoter: bind transcription factors
*regulatory: distal and proximal
B. Trans-acting elements- proteins, transcription factors
*general: required for initiation
*specific: regulate how much to transcribe - Steroid hormone regulation
A. Binds nuclear receptor -> Zn finger DNA binding domain
B. Hormone-receptor complex interacts w/ specific regulatory DNA sequence
C. Complex + coactivator protein control transcription of specific genes
Eukaryotic post-transcriptional regulation
- Alternative splicing
- Alternative polyadenylation
- MRNA editing
- MRNA stability
- RNA interference
Alternative splicing
Some exons spliced out of mRNA strands
- still functional
- accounts for vast number of proteins
- ex: tropomyosin has tissue specific isoforms
Alternative polyadenylation
- mRNA w/ different 3’ ends, altering
- Ex: IgD and IgM production
- membrane bound IgM has phobic end
- secreted IgD has philic end
*mRNA editing
One base altered
- Pre-mRNA deaminated at one base -> mRNA (altered)
* premature stop -> shorter protein
Ex: liver and small intestine produce apo Bs of different length
*apo B used as scaffold for apoproteins
*mRNA stability
Life of nRNA shortened/extended in cytosol
Ex: regulation of transferin receptor protein (TfR) expression by iron
RNA Interference
Mechanism of dec. gene expression
- Repressing translation
- Inc. degradation of specific mRNAs
Mediated by:
- Endogenously (miRNA)
- Exogenous (siRNA)
Roles:
- Cell proliferation, differentiation, and apoptosis (miRNA)
- Research tool
- Therapeutic potential
Phosphorylation
Inhibits translation
*eIF-2 + ATP -> eIF-2-P + ADP
Post-translational regulation
Important because functional product is needed
- Phosphorylation
- Glycosylation
- Hydroxylation
- Carboxylation
- Biotinylated enzyme
- Farnesylated protein
Epigenetic regulation
- Chromatin change from
* development
* environmental chemistry
* drugs/pharmaceuticals
* aging
* diet - May result in:
* cancer
* autoimmune disease
* mental disorders
* diabetes
Variations in DNA
- Transposition
2. Rearrangements in DNA
Transposition
Transposons (Tn) move randomly on dame or different chromosomes
- enzyme mediated (transposase)
- movements can be:
- Direct: cuts out and inserts Tn at new site
- Replication: Tn copied and copy is moved
- role: genome structural variation
Clinical correlations:
- Duchenne muscular dystrophy
- Hemophilia A (rare)
- Antibiotic resistance in bacteria
