Chapter Three Flashcards
What is meant by “cancer cells display altered gene expression”
They mess with the quantity, timing, or localization of oncogenes and tumor suppressor genes.
Could be the result of transcription factors
How much of the entire genome is is transcribed vs. turned into proteins?
70 percent is transcribed, but only 2% codes for proteins.
What type of RNA is important for gene regulation?
non coding RNA
Where are most single nucleotide polymorphisms found in cancer?
non-coding regions
What is epigenetics?
They are heritable changes in the gene expression that are encoded by changes in the genome and chromatin components (histones) BUT NOT actual changes in the DNA sequence
How is gene expression altered?
By regulating:
- Transcription
- Chromatic structure
- Post transitional mechanisms
What are transcription factors?
They are proteins that bind to the promoter region and regulate transcription.
They can regulate signaling involved in apoptosis, differentiation and cell growth.
What are domains?
They are distinct, independent structural / functional units of a protein.
How do we regulate transcription?
- Synthesis - regulating the genes for TFs (regulate regulators)
- Covalent modulation (turn protein on/off
- Ligand bonding (flex, weaker bonding)
- Cell localization - where is the factor at in the cytoplasm?
- Dimerization - need a pair to work
What does AP-1 transcription factor regulate?
What is it activated by?
What does it bind to on the DNA sequence?
It regulates the expression of genes involved in differentiation, growth, and death.
It is activated by growth factors, ROS, and radiation
It binds on what is called the TPA response element
What do steroid hormones regulate?
They can also regulate transcription. Here’s how:
These lipid-soluble signaling molecules will bind to what are called steroid hormone receptor superfamily, which act as ligand-dependent transcription factors.
Once a steroid hormone binds to them it will be able to bind to DNA using its Zn finger binding domain.
Where do steroids come from? How does the receptor get to the DNA?
They pass through the cell membrane and bind to intracellular receptors.
The receptors may be within the cytoplasm or on the nucleus.
Then the receptor gets to the nucleus if it is not already there and binds to DNA response element to activate transcription.
What is the histone core?
It is an octomer of histone proteins 2x (H2A, H2B, H3, and H4) that are the protein that is the bead of the “bead on the string”.
What is the secondary and tertiary structure of the chromatin that you know so well?
Secondary - 30nm fibers
Tertiary - radial loops
How does chromatin structure facilitate the regulation of gene expression?
Well, chromatin cannot just be read / transcribed if it is compacted.
The conformation that chromatin takes on is dependent on the epigenetic modifications that have been passed on.
Explain in more detail the epigenetic alterations that alter transcription and the possible consequences.
Histones may be modified as well as the DNA itself (being methylated)
These modifications will determine whether or not the chromatin is loose or tight.
Important example: if there is epigenetic silencing of the genes involved in differentiation, cells may remain as stem cells.
What are the ways that histones may be modified in post transcriptional regulation?
- Methylation
- Acetylation
- Phosphorylation
- Ubiquitination