Unit 2: 16

Question 0

What type of mutation of p53 leads to disease?

Answer 0

loss-of function mutations lead to a variety of cancers
-normal p 53 protein binds DNA and functions as a transcription repressor most likely by down regulating genes that promote cell growth

Question 1

What is DNA site recognition determined by?

Answer 1

Amino acid base pair interactions

• typically side chains from AA in recognition helix interact with major groove (usually H bonds)
• reconition helicies differ in AA sequence and thus provide “sequence specificity”
• multiple side chains contacts needed for sequence specificity
• recognizes side chains does not interrupt base pair bonding

Question 2

Define polycistronic and what type of cells show this characteristic?

Answer 2

polycistronic is multiple proteins from a single mRNA

bacterial cells

Question 3

Define operon

Answer 3

a cluster of bacterial genes transcribed from a single promoter

Question 4

what does constituitive mean

Answer 4

always on- always being expressed

Question 5

Activator proteins

Answer 5

function is opposite of repressor

• they act on weak promoters that are only marginally functional at binding RNA polymerase
• upon binding to recognition site near rooter activators help recruit and or stimulate RNA polymerase to begin transcription

Question 6

Describe how eukaryotic transcription factors are modular

Answer 6

they work as independent units -
the two main functions DNA binding
and either repression/or activation are separate encoded in different protein domains

Question 7

How does the modular nature of transcription factors affect evolution and disease? give an example

Answer 7

modularity means that fusion of different parts of different factors, say as a result of chromosomal translocation can result in a novel activity sometimes with negative consequences
-such as in leukemia
25% of pre-B-ALL t(1:19) translocation: protein fusion converts Pbx11 into a potent activator

Question 8

What are enhancers in eukaryotes, where are they and why?

Answer 8

enhancers are regulatory (cis) sequences in DNA that can be thousands of base pairs away from the promoter
-DNA loops explain why a sequence so far away can impact a given promoter.
upstream regulation of eukaryotic genes typically have multiple sites for different activators or repressors
- enhancers can also be located downstram of genes

Question 9

Besides recruiting RNA polymerase II what else can transcription factors do?

Answer 9

Transcription factors can also recruit chromatin modifying enzymes that help “loosen up” chromatin to allow access to polymerase machinery
-nucleuosome remodeling complexes use energy from ATP hydrolysis to move nucleosomes

Question 10

What are the two major types of chromatin modifications ?

Answer 10

1. covalent histone modifications

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

Question 11

What are the four major histone modifications

Answer 11

acetylation
de-acetylation
methylation
phosphorylation

Question 12

what does acetylation do to genes

Answer 12

activates

Question 13

What does de-acetylation do to gene s

Answer 13

repression

Question 14

methylation

Answer 14

activates or represses

Question 15

phosphorylation

Answer 15

coupled to acetylation

Question 16

inhibiting histone deacetylates is proving effective to treat what disease?

Answer 16

cancer - you are inhibiting a repressor therefore activating the enzymes of apoptosis like p53 that can get mutated -reactivating genes to make these proteins properly

Question 17

packaging of promoter DNA into chromatin can affect initiation of what process

Answer 17

Transcription- gene regulatory proteins and RNA poly need to access DNA that is packaged into nucleosomes.
-nucleuosomes can prevent the intiation of transcription if they are positioned over a promoter.

Question 18

what is a main consequence of the fact that there are 1800 transcription factors that regulate 30,000 genes and most regulate more than one gene

Answer 18

may be the root cause of side effects of some drugs

Question 19

list some ways in which transcription factors themselves are regulated

Answer 19

covalent modification including: phosphorylating, intracellular trafficking or selective degradation,

Question 20

what is the underlying cause of the development of different cell types

Answer 20

the expression of different transcription factors

Question 21

define gene expression profiling

Answer 21

the measurement of the mRNA abundance as measured y DNA microarray of thousands of genes at once, to create a global picture of gene expression and hence cellular function
can reveal disease such as cancer and how cells react to a particular treatment

Question 22

define Locus of control region and give an example

Answer 22

a unique regulatory region that controls chromatin structure over the entire domain
b like globin cluster to make hemoglobin

Question 23

cell memory is often transmitted through what transciptional methods

Answer 23

autoregulation
epigenetic inheritance via modification of
-chromatin
-DNA

Question 24

define autoregulation

Answer 24

txn factor activates other genes, but also its own gene

can be super bad if you get mutation fucks up its own regulation and then cannot activate anything else bc it itself is not active

Question 25

what is another name from modification of DNA itself

Answer 25

“imprinting” -prevalent in mammals and silences genes