Regulation of Gene expression

Question 1

Regulation of gene expression occurs at what stage?

Answer 1

1) chromatin structure
2) transcription initiation
3) transcript processing
4) mRNA stability

*regulation occurs at each step*

Question 2

What is a constitutive gene?

What is an inducible gene?

Answer 2

constitutive genes = essential and necessary for life therefore are continuously expressed, such as those enzymes involved in metabolism/DNA repair or those regulating transcritpion and translation - they are alwyas being made

inducible genes= many genes/proteins only synthesized when required , determines development and tissue specificity - allows cells to repsond to environment - transduced signal drives transcription

Question 4

What determines which genes are expressed?

Answer 4

availability/accessibility of gene within the chromosome

availability of proteins that promote transcription (transcription factors)

Question 5

are histones positively or negatively charged?

Answer 5

histones are positively charged

DNA is negatively charged

so DNA and histones have ionic attractions

Question 6

histone tails are rich in what residue?

Answer 6

Lysine residues

Question 7

if the chromatin is acetylated, whtat does that mean?

Answer 7

it means that the normal positive charge of the chromatin is made neutral by the acetyl group- therefore the DNA does not have the same Ionic attraction to it here and the DNA unwinds - becomes available for transcription

Question 8

What are HDACs?

Answer 8

they are repressors- HDACs

Question 9

when we inhibit HDAC, what happens?

Answer 9

when HDAC inhibitied, decondensation of chromatin occurs and activation of silenced genes occur- induction of cellular differentiation or cell death

HDAC inhibitor (vorinostat) is FDA approved for cutaneous T-cell lymphoma

Question 10

What are the 3 general regions of a gene?

Answer 10

1. promoter region - transcriptional start site
2. coding region - eukaryotes- introns and exons
3. 3’ UTR- important for mRNA stability and determines half life of mRNA

Question 12

what is the promoter region of a gene? what types of promoters are there?

Answer 12

promoter sequences - act as a regulatory element upstream of the start site of a gene - each gene has a unique promoter -

2 types

basal promoter element - bound to RNA pol2 and basal transcription factors - required for RNA pol 2 binding

Enhancer element - recognized by proteins that will aid transcription - transcription factors

Question 13

What are the two different types of basal elements?

Answer 13

• TATA box- most common - can bind basal TFs and RNA pol 2 on own strong element
• CCAT box - less common and not as strong - needs help of coactivator to bring in Transcription factors and RNA pol 2

Question 14

What are transcription factors?

Answer 14

Transcription factors are proteins that bind specific DNA sequences - they recognize the response/enhancer element -they control the rate of transcription

Question 15

what must the transciption factor bind to ‘turn on’ the transcription of the gene?

Answer 15

the transcription factor must bind to promoter/ enhancer

Question 16

how is the transactivation domain usually regulated?

Answer 16

the TAD is usually regulated by phosphorylation of specific residues of TAD

Question 17

what regulates the rate of transcription of a gene?

Answer 17

the amount and activity of transcription factors regulates the rate of transcription

so the number of binding sites for that transcription factor in a promoter determines the rate of transciption

Question 18

what part of mRNA encode the protein coding region of the gene mRNA?

Answer 18

the exons

Question 19

What are the main areas of post-transcriptional regulation?

Answer 19

1. mRNA stability
2. differential mRNA splicing

Question 20

what determines mRNA stability?

Answer 20

mRNAs from different genes have their longevity encoded within them

the 3’ UTR sequence determines the stability of mRNA (Poly A tail)

Tail gradually shortened over lifetime of mRNA

Question 21

what do you cal the process of rearranging/cutting out exons/introns?

Answer 21

splicing and exon shuffling

Question 22

what are miRNAs?

Answer 22

small strands of RNA that regulate gene expression - transcribed from the DNA but non-coding they don’t make any proteins

they partially complementary to a number of mRNAs they bind to them and down regulate gene expression - promote RNA degradation - binds to complementary sequences in 3’ UTR and induces degradation - binds mRNA and blocks translation