Chapter 13 Flashcards
Mechanisms of gene regulation in eukaryotes before transcription
- Regulatory proteins
- Regulatory sequences (enhancers, silencers)
- Chromatin structure
- Alternative promoters
- Methylation
Mechanism of gene regulation in eukaryotes after transcription
- Alternative 5’ capping
- 3’ polyadenylation
- splicing
Mechanisms of gene regulation in eukaryotes after splicing
- Small RNAs that influence mRNA stability
- Other factors that influence mRNA transport and stability and the initiation of translation
Mechanisms of gene regulation in eukaryotes in the cytoplasm, after export of the mature mRNA
- Factors that influence the initiation of translation
Mechanisms of gene regulation in eukaryotes in the cytoplasm, after translation
- Posttranslational modifications
- Binding of regulatory molecules
- Regulation of protein stability
Variation in cis-element regulator elements
- In single celled eukaryotes, cis regulatory elements are usually upstream and near the start of transcription
- In multicellular eukaryotes, cis regulatory elements may be upstream, downstream; near or far
Sonic Hedgehog in mammals
- Two enhancers: one for brain cells and one for limb cells
- the one for brain cells is near the start of transcription
- the one for limb cells in 1 million bp upstream in the intron of another gene
- Regulation of SHH is modular and depends on what transcription factors are expressed in each cell
Conservation of enhancer sequences
- Enhancer sequences can be highly conserved among diverse organisms
- Natural selection
What is a nucleosome
- a segment of DNA wound 2x around 8 histone proteins
- Not static - can dissociate from DNA, move, translocate to different sections of DNA
Euchromatin
region that is more accessible
Heterochromatin
region that is less accessible
Facultative heterochromatin
Accessible to transcription when there are reversible changes in nucleosomes
What causes variation in accessibility of chromatin
- Cell type
- Developmental stage
- Environmental conditions
What influences accessibility of chromatin
- Chemical changes in DNA
- protein
Important features of epigenetic modification
- chromatin structure change
- Transmissible during mitosis
- Reversible
- Affects transcription
- Does not alter nucleotide sequence of DNA
Positive effect variegation
Change in expression due to change in location of heterochromatic region that partially prevent expression
- no change in sequence
Varigated eye
- su(var) - Mutations that reduce heterochromatin partially restore the wildtype phenotype
- E(var) - Mutations that increase heterochromatin make the mutant phenotype more extreme
How are genes made available for transcription in eukaryotes
- Gene may be inside euchromatin where chromatin is open and expression is largely continuous
- Proteins called chromatin remodelers may change the distribution or composition of histones to make transcription temporarily possible
- Proteins called chromatin modifiers may add or remove acetyl or methyl groups to make transcription temporarily possible
Chemical modification of chromatin
- Proteins that add chemical groups to histones are called writers; those that remove them are called erasers
- Proteins that bind to these groups are called readers
Histone Acetyltransferase
chromatin writers that add acetyl groups; addition of acetyl groups makes protein less positive charged and less strongly attracted to DNA
Histone deacetylase
Erasers that removed acetyl groups
Histone methyltransferase
Chromatin writers that add methyl groups; methylation can open or close chromatin
Histone demethylases
Erasers that remove methyl groups
DNA methyltransferase
Add methyl groups to DNA nucleotides; repressed expression
Epigenetic heritability
- Chromatin structure is broken down during DNA replication
- During mitosis, some histones are repackaged after replication; these influence the epigenetic state of newly translated histones
- During meiosis, most epigenetic marks are lost - some passed to the next generation
Insulator sequence
cis-acting sequences that influence the ability of enhancers to initiate transcription
Open promoters
promoters not bond by histones - nucleosome depleted region
- no TATA box
Covered promoters
- Genes with tissue specific, developmental-specific, environmentally induced expression
- blocked transcription until nucleosome is removed
- contian TATA boc and other transcription-factor binding sequences
-active competition between nucleosomes and transcription factors for binding
Pioneer factors
initiate and recruit activators and repressors to enhancer and silencer respectively
Chromatin remodeling
- Genes within facultative heterochromatin are expressed when trans-acting factors cause changes in nucleosome structure, chemistry and composition
