Lecture 17: Gene Regulation

Question 1

What do txn reg proteins have in common?

Answer 1

usually contain recognition alpha-helix, which inserts into the major groove of DNA and makes multiple contacts

Question 2

What kind of interactions determine DNA site recognition? What kind of bonds are predominantly formed?

Answer 2

AA-base pair interactions

H-bonds

Question 3

What is the repressor molecule in the Trp operon? Where does it bind?

Answer 3

Trp

Operator

Question 4

Where is the operator in an operon located?

Answer 4

Within promoter

Question 5

What is an operon? What kingdom has this?

Answer 5

clustered genes, coordinately regulated

Question 6

To what sequence does a repressor protein in an operon bind?

Answer 6

operator

Question 7

What does polycistronic mean? Where is this found?

Answer 7

multiple distinct proteins can be made from single mRNA

bacteria operon

Question 8

The operator is a ____-acting sequence in an operon

Answer 8

cis

Question 9

what is constitutive expression?

Answer 9

only transcribed when needed

Question 10

Txn factors are modular. What does this mean? What is the result?

Answer 10

DNA binding domain can bind independetly of repressor/activator domain
novel activity

Question 11

How does txn factor modularity result in novel activity?

Answer 11

can have fusion of different parts with different txn factors
ex. xs translocation

Question 12

Euk txn regulators bind ______ and stimulate ______

Answer 12

enhancers

RNA Pol II

Question 13

How can aeukaryotic enhancer be far away from a promoter, but still affect txn?

Answer 13

looping

Question 14

What three molecules must bind to activate euk txn?

Answer 14

txn factors (activator protein)
Mediator
Rna Pol

Question 15

activators in eukaryotic txn acts through ______ to recruit ______, and can also recruit ______ modifying enzymes

Answer 15

intermediary proteins ex. mediator complex
Rna Pol complex
Chromatin

Question 16

Where do euk enhancers work? What allows this to happen?

Answer 16

upstream, downstream, or within gene

looping

Question 17

What does overexpression of HOX11 gene cause? What is HOX11?

Answer 17

T-cell actue lymphoblast leukemia

T-cell gene enhancer

Question 18

What needs to happen to chromatin before txn can occur?

Answer 18

needs to loosen up

Question 19

what two major types of chromatin modifications can be done to loosen chromatin and allow txn?

Answer 19

1. covalent histone modifications

2. ATP-dependent nucleosome remodeling (move, slide, exchange)

Question 20

what does acetylation of a histone do?

Answer 20

activate txn

Question 21

What does de-acetylation of a histone do?

Answer 21

repress txn

Question 22

What are the 4 possible histone modifications? What structures are modified?

Answer 22

Residues are modified
acetylation/de-acetylation
methylation
phosphorylation

Question 23

What are the 2 ways in which euk gene activator proteins increase the rate of txn initiation?

Answer 23

1. act directly on txn machinery

2. change local chromatin structure

Question 24

What do histone acetyltransferases (HATs) do? What do histone deacetylases (HDACs) do?

Answer 24

HAT - hyperacetylate chromatin (activate gene exp)

HDAC - hypoacetylate chromatin (deactivate gene exp)

Question 25

what is steroid receptor (glucocorticoid receptor - GR)? does it act on one or multiple genes?

Answer 25

txn factor

multiple genes

Question 26

The fact that each regulator targets multiple genes can be the root cause of _______

Answer 26

drug side effects

Question 27

What are 7 activities which regulate synthesis and activity of txn factors?

Answer 27

1. protein synthesis (feedback)
2. ligand binding
3. covalent modifications (phos)
4. add’n of 2nd subunit
5. unmasking - remove something
6. stimulation of nuclear entry - remove inhibitory protein, can enter nucleus
7. release from membrane

Question 28

What underlies the development of different cell types? What can happen when this doesn’t happen successfully?

Answer 28

exp of different txn factors

cancer

Question 29

What is gene expression profiling? What techniques does it use? what is the clinical use?

Answer 29

• measures abundance of mRNA in cells or tissues
• DNA microarray, RNA seq, cluster analysis
• link expression patterns to clinical outcomes, pharm effects

Question 30

What is the Hb tetramer composed of?

Answer 30

2 alpha, 2 beta subunits

Question 31

What are the only 3 places where Beta globin is produced?

Answer 31

adults
bone marrow
erythroid cells

Question 32

What is the locus of control region? What does it do?

Answer 32

shared control region for ALL beta globin like genes in a cluster

Question 33

How does the beta globin gene cluster differ in different cells?

Answer 33

euchromatin where expressed

heterochromatin in cells where not expressed

Question 34

What is the result of deletion of the locus of control region?

Answer 34

silences entire cluster for beta globin production

beta thalassemia = severe anemia

Question 35

What is the cell memory mechanism of autoregulation?

Answer 35

txn factor activates its own gene in add’n to other genes

Question 36

What happens in the cell memory epigenetic mechanism of modification of histones?

Answer 36

acetylated or methylated state of chromatin is passed from parental cell to daughter cells
keeps genes expressed at similar levels across cell generations

Question 37

What happens in the cell memory epigenetic mechanism of modification of DNA?

Answer 37

methylated DNA attracts histone modifiers

leads to txn repression