Regulation of gene expression
Introducido| English | Significado |
|---|---|
| transcription factor/trænˈskrɪpʃn ˈfæktə/ | A protein that binds specific DNA sequences or interacts with transcription machinery to regulate gene expression. |
| enhancer | enhancer |
| chromatin | chromatin |
| methylation/ˌmeθɪˈleɪʃn/ | methylation |
| epigenetics/ˌepɪdʒɪˈnetɪks/ | The part of that access that is passed to daughter cells without changing the sequence. |
| nucleosome | nucleosome |
| epigenetic | epigenetic |
Same genes, different cells
- Almost every cell carries all of your ~20 000 genes. A neuron is a neuron because of which genes are on, when, and how much.
- That control layer is where evolution works fastest, and where much disease starts.
The control stack
- Transcription factors 转录因子 bind the promoter at the start of a gene, and enhancers 增强子 that can sit 100 kb away. DNA loops bring the enhancer to the promoter.
- Only about 1.5% of the genome codes protein; regulatory sequence is far larger.
How does an enhancer differ from a promoter?
Dificultad 1/5 · 100 monedas + un pequeño bono en el primer intento de hoy
Enhancers loop to the promoter from up to about 100 kb away, in either orientation; the promoter sits at the start site.
Chromatin decides access
- Chromatin 染色质 state gates the DNA: histone marks open or close it, and CpG methylation 甲基化 keeps it shut. In a mature cell 70–80% of CpG sites are methylated.
- Epigenetics 表观遗传学 is the part of that access that is passed to daughter cells without changing the sequence.
Match each term to what it does.
Dificultad 2/5 · 140 monedas + un pequeño bono en el primer intento de hoy
Sequence elements (promoter, enhancer), the proteins that read them (factors) and the marks that gate access (methylation) work together.
Why factors work in teams
- A factor reads about 6–8 bases. A random 6-mer turns up every $4^{6} = 4096$ bp, about 800 000 times on each strand of the 3.2 Gb genome: far too often to mean anything.
- Several factors binding side by side multiply the odds against a chance match, like a longer password. Enhancers are team logic gates.
Why can a single 6-base motif not regulate genes cleanly?
Dificultad 1/5 · 100 monedas + un pequeño bono en el primer intento de hoy
4⁶ = 4096, so a 6-mer hits about every 4 kb. Several factors cooperating is what buys specificity, like a long password.
A factor reads 8 bases. About how many chance matches are there on one strand of a 3.2 Gb genome, in thousands?
Dificultad 2/5 · 140 monedas + un pequeño bono en el primer intento de hoy
4⁸ = 65 536, and 3.2 × 10⁹ / 65 536 ≈ 48 800, about 49 thousand: two more bases cut the matches 16-fold, but still far too many alone.
Packing two metres
- The 2.2 m of DNA wraps around nucleosomes 核小体 (about 200 bp each), about 7-fold shorter, then folds into a ~30 nm fibre, about 40-fold.
- Loops and further folding bring a mitotic chromosome near $10^{4}$-fold. Packed regions are hard for factors to reach.
Put the packing stages in order, from least to most compact.
Dificultad 3/5 · 200 monedas + un pequeño bono en el primer intento de hoy
About 7-fold, then about 40-fold, then near 10⁴-fold overall in a mitotic chromosome.
Worked example: drinking milk as an adult
- In most people the lactase gene (LCT) switches off after weaning. Many northern Europeans carry one base change about 14 kb upstream, inside an intron of a neighbouring gene.
- That base creates a stronger enhancer, so LCT stays on and adults digest milk. No protein changed, yet the trait spread across a continent.
Lactase persistence is caused by a change in the lactase enzyme's amino acids.
Dificultad 1/5 · 100 monedas + un pequeño bono en el primer intento de hoy
The change is one regulatory base about 14 kb upstream that strengthens an enhancer; the enzyme itself is unchanged.
Worked example: twins who differ
- (Fictional) identical twins share a disease gene, but one is much sicker. In that twin, the gene's promoter is methylated; in the other it is not.
- Same letters, different access: an epigenetic 表观遗传的 modifier of severity. This is why methylation tests sit beside sequencers in the diagnostic lab.
Why can identical twins have different severity of the same genetic disease?
Dificultad 1/5 · 100 monedas + un pequeño bono en el primer intento de hoy
Epigenetic marks pass through cell divisions yet can be reset; they are an access layer on top of the same letters.
Three common slips
- "Epigenetic means permanent." Marks pass through divisions but can be reset.
- "An enhancer is just a promoter." Enhancers work at a distance and in either orientation; the promoter sits at the start site.
- "Genes are ON or OFF." Expression is graded, and set by tissue and time.
Once a promoter is methylated, it can never be switched back on.
Dificultad 1/5 · 100 monedas + un pequeño bono en el primer intento de hoy
Methylation passes through divisions but can be removed or reprogrammed, as happens in early embryos and with some drugs.
Recap
- ~20 000 genes, ~1.5% coding; enhancers loop to promoters and act as team switches.
- Methylation (70–80% of CpG) and histone marks gate access and pass to daughter cells.
- One regulatory base can change a trait without changing a protein.