8.17.16 Lecture Flashcards
___ gene control is the norm for eukaryotic cells.
Combinatorial
Multiple different regulatory proteins can bind to ___ regulatory elements in a gene.
Identical
The specific combination of proteins that bind to an element is dependent on what?
The cell type or physiological state of the cell
The probability of initiating transcription results from what?
The net effect of all the interactions of promoter inputs
What is the general role of Mad, Max, Myc?
Control genes involved in cell division
What does the heterodimer Myc-Max do?
Activate transcription via histone acetylation, leading to cell proliferation
What does the homodimer Max-Max do?
Repress transcription - basal level
What does the heterodimer Mad-Max do?
Silence transcription via histone deacylation, leading to cell differentiation
What type of transcription factors are Mad, Max, and Myc?
Basic Helix-Loop-Helix transcription factors
What does the basic region of a transcription factor do?
Bind DNA
Myc has a ___ activation domain; Max has ___ activation domain.
Large; no
Myc is only expressed in…
…the G1 to S transition
What are the basic methods of regulation of gene expression?
- Activation of transcription factors and induction of gene expression.
- Changes in chromatin structure
- Epigenetic mechanisms
What are the various methods of activation of TF?
- Protein synthesis of TF
- Ligand binding
- Covalent modification (phosphorylation, etc.)
- Complex between DNA-binding and activation subunits
- Unmasking (remove inhibitor by phosphorylation)
- Stimulation of nuclear entry by removal of inhibitor
- Release from membrane by proteolysis
___ can trigger signaling pathways to initiate gene expression. Give an example of this.
Extracellular signals; kinase cascades
Why are cascades utilized?
Signal amplification
Describe the c-Fos/c-Jun AP-1 element kinase cascade.
- JNK, a terminal kinase from the cascade, phosphorylates Jun. ERK, a terminal kinase from the cascade, phosphorylates Fos.
- Jun and Fos heterodimerize through leucine zippers and bind with the scissor motif to the AP-1 element.
How is gene expression inhibited by changes in chromatin structure? Give an example of this.
Positioning a gene in heterochromatin inhibits gene expression; inactivation of the X-chromosome.
Describe the process of inactivation of X-chromosomes.
- Both X genes are active.
- A randomly selected X is condensed and inactivated early in development (becomes a Barr Body) by deacetylase and methylase.
- This is passed on in inheritance.
Where does the signal for inactivation of X-chromosomes come from?
Placenta
Heterochromatin structure regulates ___ gene expression on Chromosome ___.
Hemoglobin; 11
Define epigenetics.
The passage of information from parental cells to progeny by a mechanism other than DNA sequence instructions.
Is it possible for two alleles to have the same nucleotide sequence and give different inheritable genetic information?
Yes - via epigenetic information
Epigenetic modifications occur through modification of either ___ or ___.
DNA or gene regulatory proteins
What happens in a positive feedback loop?
- Transient signal turns on expression of a gene.
- Transcription factor is produced, binds to a regulatory element upstream of the gene and promotes continued transcription. This gives a cell “memory.”
Combinatorial gene control and positive feedback loops work together in ___.
Embryonic cell development
Embryonic cells receive signals from the placenta ___.
Asymmetrically
What does DNA methylation do?
Methylation of a promoter or enhancer region usually inhibits expression (does not disrupt hydrogen bonds) by preventing TF binding.
The methylated sequence is ___.
Palindromic
How is DNA methylation inherited?
An established pattern of DNA methylation is continued in the progeny by methyl-directed methylating enzymes (maintenance methyl transferase), which act at hemimethyl sites.
How does methylation upstream of a transcriptional start site block transcription?
By interfering with binding of TF and RNA polymerase and/or by promoting binding of inhibitory proteins
What do CpG islands do?
Protect essential genes from DNA methylation; areas with a high concentration of C and G are resistant to methylation.
How is histone acetylation maintained?
Maintenance acetylases acetylate histone proteins of nucleosomes that are hemi-acetylated in progeny cells.
What is imprinting?
Retention of methylation in progeny cells
Genomic imprinting occurs in ~___ genes.
50
Usually, the ___ gene is not expressed; the ___ gene is expressed.
Hypermethylated; hypomethylated
Imprinting is ___-dependent.
Sex; the gene retains methylation in the sperm or the egg (not both)
What does imprinting lead to?
Sex-dependent non-Mendelian genetic expression of the imprinted gene; a functionally haploid cell.
Imprint “on” = ___. Imprint “off” = ___.
Normal copy; not expressed (methylated)
When are imprints erased?
During germ-cell formation, but before meiosis
When are imprints reimposed?
In a sex-specific pattern later in germ-cell development
