Eukaryotic Gene Regulation Flashcards
1
Q
describe cis regulatory elemtns
A
- DNA binding sites
- transcription factor binding site or enhancer binding site
- ON THE DNA ITSELF
2
Q
describe trans regulatory elements
A
- Modify the expression of genes distant from the gene that was originally transcribed to create them
- These are typically proteins such as TFs/enhancer binding proteins
- can have positive or negative effects
3
Q
name cis elements
A
- Basal promoter sequence
- bind the general transcription factor proteins which are associated with RNA pol
- Proximal control regions
- these bind TF proteins and are found near promoter
- Enhancer sequence
- found far away from the promoter (usually 5’ upstream)
4
Q
describe the basal promoter region
A
- includes TATA and CAAT box
- not much regulation involved
- responsible for interaction with the general TFs which directly recruit RNA pol II to promoter
- termed the basal transcription apparatus
5
Q
name 3 trans elements (transcription factors)
A
- DNA binding domain
- TFs have DNA binding domains that only bind to certain DNA sequences
- Dimerization domain (Glucocorticoid, HIF1α and HIF1B)
- 2 TFs bind together to form a functional DNA binding unit called a dimer. Formation of a dimer adds an extra element of complexity and versatility
- Activation/repression domain (myc/max)
- binds to enhancer binding proteins or other TF factors and modulates their function
6
Q
describe “competition” of repressor proteins
A
- competition for enhancer sequence: binding between activator and repressor proteins
- Binding of repressor to enhancer sequence competes for the DNA binding site (cis-element) of the activator
- Repressor proteins may reduce transcription levels through competition
7
Q
describe “quenching” of repressor proteins
A
- Quenching occurs when a repressor protein binds to and interferes with the DNA-binding domain of an activator protein
- now the activator cannot bind to enhancer sequence
- repressor proteins may reduce transcription through quenching
8
Q
describe “blocking” by repressor proteins
A
- blocking occurs when the repressor protein binds to the activation domain of an activator protein and prevents it from interacting with the basal transcriptional machinery
- repressor proteins may reduce transcription levels through blocking
9
Q
describe response elements
A
- response elements are short sequences of DNA within a gene promoter region that are able to bind a specific transcription factor and regulate transcription of genes
- all genes that contain a specific response element will be regulated in a similar fashion
10
Q
describe the hypoxia inducible factor
A
- most, if not all, oxygen-breathing species express the highly-conserved transcriptional Hif-1
- heterodimer
- Hif-1 allows a coordinated cellular response to low oxygen tension
11
Q
describe the hypoxia response elements
A
- HIF1α and HIF1ß transcription factors must dimerize, then bind DNA sequences to regulate expression of many different genes
- 5’ TACGTG 3’
12
Q
describe HIF1α
A
- HIGH O2: HIF1α is hydroxylated and degraded by proteasome
- Low/No O2: HIF1α stabilized, moves to the nucleus and dimerizes with HIF1ß to activate multiple genes that enhance O2 delivery to tissues and/or energy supply via glycolysis
13
Q
what is the hypoxia event sequence an example of?
A
- Induction of expression of a family of genes by transcription factor binding to a common enhancer sequence of many different genes
14
Q
HIF as a therapeutic target?
A
- Solid cancers are quick growing and hungry–they are often hypoxic
- learning how to inhibit HIF1α/HIF1B mediated gene expression may provide a way of selectively killing tumors
15
Q
describe the glucocorticoid receptor
A
- the glucocorticoid receptor (GR) is a zinc-finger type TF
- the activated GR complex up-regulates the expression of anti-inflammatory genes in the nucleus and represses the expression of pro-inflammatory proteins in the cytosol
