Flashcards in Lecture 18 - Introduction to control of gene expression Deck (14):
Human genome contains 50000 genes.
Only 10000 genes are expressed.
Genome is identical in every cell.
Must be differentially interpreted in diff cells at diff times.
Human cells all contain the same genetic blueprint.
Differential gene expression is tightly regulated in.... (3)
Development , embryo/adults
In response to hormones, infections
Diff tissues/cell types express diff genes (brain vs muscles)
Failure to regulate gene expression tightly may lead to... (4)
DNA --> RNA --> Proteins
Metabolism --> Metabolic disease (e.g. diabetes).
Cell shape/motility --> Metastasis.
Cell differentiation --> Congenital disorders (e.g. drosophila).
Cell proliferation --> Cancer.
Drosophila homeotic mutants (5)
BX-C (Bithorax complex- type of homeotic gene) controls the differentiation of abdominal/posterior thoracic segments.
Located on chromosome III.
Genes mutate and the third thoracic segment creates a 'second thorax' --> 2nd pair of wings/stomach.
Antennapedia (Antp) is a HOM-C gene - controls the formation of legs during development.
Loss of function mutations OR gain-of-function mutations convert antennae into ectopic legs.
Differentiation from a single cell (2)
• Totipotent cells – only found in the zygote, can differentiate into any cell.
• Pluripotent- can form any tissues in body except placenta tissue.
The big goal (2)
Isolate adult stem cells from all developmental compartments.
These cells develop in vivo or in vitro in a controlled manner so we can regenerate tissues.
Insufficent expression of B globin gene..
The B globin gene is structurally normal, mutations in actual bases. Single base changes.
ATAAA --> ACAAA (T--> C)
CACaGCTCCT --> CACgGCTCCT ( A--> G)
Examples of translational control (3)
Early embryogenesis - during first 4-8 cell divisions no gene expression. End of blastocyst formaton, first genes expresssed are from MATERNALLY-DERIVED PRE-FORMED mRNA.
Environmental stress - Exposure to heat shock/pathogens cause change in translation.
E.G. Ferritin (shows how much iron the body stores).
Anatomy of Eukaryotic mRNA (4)
Frame is set by first codon - always AUG.
5' UTR part of exon.
Kozak consensus sequence - major role in initiation of translation.
Sequence on mRNA molecule (recognised by ribosome) initiates translation.
5'/3' UTRs and control of gene expression (6)
5' UTR - How efficiently the ribosome initiates translation.
Globin - Effectively translated.
Ferritin - Uneffectively translated.
3' UTR - Stability on mRNAs.
Globin - Very stable.
Immune stress hormones - Very unstable.
Intracellular Iron levels are translationally controlled
Ferritin - binds Iron and retains in the cytoplasm as a store for excess.
Only need Ferritin at times of Iron excess.
500 small non-coding RNAs - micro RNAs.
Transcribed by RNA Polymerase II.
Control post-transcriptional regulation of about 1/3 of all human genes.
Regulates several target genes.
Targets a complementary mRNA molecule for destruction.