Lec 5: Regulation of Gene Expression Flashcards
What controls chromatin accessibility?
DNA methylation (strong inverse correlation between DNA methylation and chromatin accessibility)
Two main ways to control gene expression?
Transcriptional control
Posttranscriptional control
What two classes of elements are involved in transcriptional control?
cis-acting elements (DNA elements adjacent to or within the gene)
activator or repressor proteins (bind DNA/interact with transcription proteins)
Binding of regulatory proteins to cis-acting elements in DNA may result in what?
may either activate or repress transcription
What gene regulation occurs at the level of chromatin?
Gene regulation can be controlled by binding of specific activator proteins (chromatin remodeling) and by acetylation/methylation of histones
What are some examples of elements associated with the core promoter of a particular gene?
BRE (TFIIB recognition element) DPE (downstream promoter element) which are located downstream Initiator element (INR) which is functionally analogous to the TATA box
At the level of transcriptional control of gene expression, what could different promoters for the same gene lead to?
- could lead to response of different promoters to various regulatory signals
- could lead to different isoforms of a particular protein (e.g. a signal activates 1 type of promoter to generate 1 isoform)
For insulin, what types of sequence elements exist that control transcription?
Both ubiquitous and tissue-specific transcription factors
Describe the steps of how NFkB controls transcription.
- TNFa binding recruits signaling proteins
- Activates protein kinase that phosphorylates and activates IkB kinase kinase (IKK)
- IKK has alpha and beta, and IKKb phosphorylates IkB, marking it for degradation
- IkB degredation releases NFkB
- NFkb goes to nucleus, stimulating transcription of target genes
What are 2 examples of transcriptional control?
Regulation of transcription by phosphorylation
REgulation by alternative promoter use (which can generate tissue specific isoforms)
What are 5 examples of post-transcriptional control of gene expression?
- alternative polyadenylation
- alternative splicing
- control of mRNA translation and stability
- RNA editing
- regulation of gene expression by RNA interference (RNAi)
How is a transcribed antibody molecule determined to be secreted or membrane-bound?
For membrane bound, intron near 3’ is removed and thus resulting in a molecule that codes for membrane-bound antibody molecule
For secreted antibody, RNA sequence is polyadenylated upstream from the intro’s 3’ splice site, so some of the intron sequence is coding creating hydrophilic C-terminal portion of molecule
How are different variants of a-tropomyosin produced in striated vs smooth muscle?
a-tropomyosin is made from the same gene, but is different in smooth muscle vs striated muscle.
alternative splicing produces the two forms
How does iron regulate ferritin and transferrin receptor translation?
Low iron -> free aconitase
Free aconitase binds to ferritin mRNA to prevent translation
Free aconitase binds to 3’ end of transferrin to prevent degradation of mRNA
High iron -> bound aconitase
no aconitase results in freely translated ferritin mRNA and degradation of transferrin receptor mRNA
How does RNA editing result in 2 forms of human apolipprotein B (ApoB) mRNA in the interstine and in the liver?
in RNA editing, a single nucleotide is substituted in the RNA
-RNA-dependent deaminases catalyze single nucleotide substitutions in the RNA, resulting in different products in different tissues
