Gene Regulation I

Question 0

How does positive regulation make more sense in highly differentiated cell systems?

Answer 0

Most genes are off until needed making fine control easier in huge genomes like ours.

Question 1

What happens to most eukaryotic genes?

Answer 1

They are silenced

Question 2

Why is heterochromatin not transcribed?

Answer 2

This is because the DNA is hyper methylated at CpG nucleotides and their histones are deacylated

Question 3

Why is euchromatin transcribed?

Answer 3

It’s DNA is hypomethylated and it’s histones are acylated

Question 4

How are histones modified when being transcribed?

Answer 4

Histone acetyl transferases (HATs) unwind DNA to promote transcription
Histone deacetylases (HDACs) reverse the process to form nucleosomes

Question 5

What happens to chromatin overall when being transcribed?

Answer 5

Chromatin relaxes, resulting in hypersensitivity to DNase treatment

Question 6

What is DNase treatment?

Answer 6

CpG islands

Hpall Tiny Fragments or HTF islands

Question 7

What does PCAF do?

Answer 7

It’s a HATs

Acetylates residues in H3 and H4

Question 8

What does NuA4 do?

Answer 8

Acetylates H2A and H4

Question 9

What does SWI/SNF do?

Answer 9

Nucleosome movement; transcriptional activation

Question 10

What does the ISWI family do?

Answer 10

Nucleosome movement; transcriptional repression

Question 11

What does epigenetic refer to?

Answer 11

Changes in phenotype without changes in genotype “heterochromatin vs euchromatin”

Question 12

What does DNA methylation do?

Answer 12

Gene silencing

Question 13

What does histone acetylation do?

Answer 13

Gene activation

Question 14

What are CpG’s considered to be?

Answer 14

Hotspots for genetic mutation

Question 15

What do methylcytosines attract?

Answer 15

Repressor proteins

Question 16

How to methylcytosines attract repressor proteins?

Answer 16

MeC in enhancer blocks transcription factor binding directly
MeC recognized by MBP, which recruits co-repressor (transcription block)
Recruited co-repressors include chromatin modifiers (HDACs, HMTs)
Intragenic methylation truncates transcription

Question 17

What regulates X-inactivation?

Answer 17

By the Xist gene transcript, transcribed from inactivated X chromosome

Question 18

What is the Xist gene?

Answer 18

A large (17kb) polyadenylated transcript with no large ORF… No protein product

Question 19

What happens to Xist once the X chromosome is inactivated?

Answer 19

Xist remains in nucleus & associates with inactivated X

Question 20

What makes deletion in region 15q11-13 different than others?

Answer 20

The genes are differentially silenced in male and female gametes

Question 21

What is Angelman syndrome?

Answer 21

Only paternal genes are expressed meaning there was a mutant maternal chromosome 15

Question 22

What is Prader-Willi syndrome?

Answer 22

Only maternal genes are expressed meaning there was a mutant paternal chromosome 15

Question 23

What are the symptoms of Prader-Willi syndrome?

Answer 23

Mental retardation
Obesity
Hypogonadism
Small hands & feet
Itchy skin
Voracious appetite

Question 24

What are the symptoms of Angelman Syndrome?

Answer 24

``` Mental retardation Hypotonia Absence of speech Large mandible Tongue thrusting Epilepsy ```

Question 25

What does folate deficiency affect during development?

Answer 25

Increases risk for neural tube defects

Question 26

What does hyperhomocysteinuria increase risk for?

Answer 26

Increases risk for cardiovascular disease

Question 27

What are some epigenetic changes that cigarette smoke causes?

Answer 27

Hypomethylation of oncogenes | Hypermethylation of tumor suppressor genes

Question 28

What are the two basic classes of genes?

Answer 28

Constitutive - essential for cell survival | Inducible/repressible - highly regulated

Question 29

What are transcription factors?

Answer 29

DNA binding proteins that regulate transcription initiation

Question 30

What do transcription factors do?

Answer 30

Recruiter for basal transcription machinery | Enhance speed and efficiency of RNA polymerase

Question 31

How much can transcription factors increase the transcription rate by?

Answer 31

By many thousand full

Question 32

What are basal factors? And what are some examples of them?

Answer 32

A transcription factor that positions RNA polymerase on the core promoter TFIID,A,B,E,F,&H

Question 33

What are activators?

Answer 33

Transcription factors that bind to enhancer elements; up rate of assembly of transcriptional machinery

Question 34

What are mediators?

Answer 34

Adapter molecules that connect activators (&repressors) to basal factors

Question 35

What are repressors?

Answer 35

Transcription factors that bind to silencer elements; interfere with activators to slow transcription or induce heterochromatin formation

Question 36

What are 3 heterochromatin modifiers?

Answer 36

HATs, HDACs, HMG proteins