LEC 5: Regulation of Gene Expression II Flashcards
DNA Methylation
Transcriptionally active genes possess significantly lower levels of methylated DNA than inactive genes
- Genes that are methylated are less active
- DNA Methylation is related to the Heterochromatin formation
Fragile X Syndrome
- FMR-1 gene encodes fragile X mental retardation protein (FMRP)
- Within this gene are CGG repeats, and when methylated the FMR-1 gene is silenced
Histone Modification: Acetylation
Acetylation by HATs and co-activators leads to euchromatin formation (active chromatin)
- transcriptionally active
Histone Modification: Methylation
Methylation by HDACs and co-repressors leads to heterochromatin formation (inactive chromatin)
- not transcriptionally active
Gene Amplification
Repeated rounds of DNA replication yield multiple copies of a particular chromosomal region
- Extra copies of genes usually result in increased level of the resulting protein
Control at Transcription Initiation
By using different sequences (promoter, enhancer or silencer sequences) and factors, the rate of transcription of a gene is controlled
- Temporal, Spatial, Time Controlled
Control of mRNA Splicing
Splicing allows a cell to ‘swap’ exons during gene expression
- Changing the way mRNA is spliced changes the amino acid sequence in the protein made from it, thus altering protein and function
- Splicing can thus regulate gene expression in eukaryotic cells depending on health of the cell
Calcitonin mRNA Splicing
Depending on how the Calcitonin gene is spliced, proteins of varying functions are produced:
- 32 AA’s: Reduces bone resorption
- 37 AA’s: Vasodilator
Splicing and Regulating Cell Survival: Bcl-x Gene
Bcl-x gene responsible for the generation of 2 distinct proteins
- Anti-apoptotic or pro-apoptotic
- Extremely important gene/signalling pathway to target in cancer and neurological disorders
Control of mRNA Stability
Different transcripts have different half-life which directly correlate to function and expression of gene
- The longer half-life of mRNA, more time for translation to occur and thus more proteins produced