Gene Expression

Question 1

TATA box/initiator sequence

Answer 1

25-35 bps upstream from start site that determine transcription initiation an direct RNA pol II to the right spot, this is also where GTFs bind

Question 2

promoter proximal sequence

Answer 2

200 bp upstream of transcription site, roughly 20 bp long, can be bound by factors in a cell type specific manner

Question 3

enhancers

Answer 3

multiple control elements, each 8-20 bp long and an entire one could be 100-200 bp long, can be 200 tens of kpbp upstream of downstream from the promoter or last exon, can even be INSIDE an intron, also work in a cell type specific manner

Question 4

transcription factor

Answer 4

protein that binds DNA to regulate what gets transcribed by recruiting or blocking RNA polymerase, can also alter chromatin structures

Question 5

Thalassemias beta

Answer 5

inherited anemia because erythroid cells don’t produce the beta-globin promoter which causes less beta-globin mRNA so less protein gets made

Question 6

thalassemias gamma delta beta

Answer 6

deletion of the locus control region (LCR) of the beta globin gene cluster

Question 7

hemophilia b leyden

Answer 7

x linked disorder that affects clotting because of mutations in the promoter of the factor IX gene, before puberty the men only have 1% of the factor but puberty causes the androgen receptor to become active– this can bind

Question 8

fragile x syndrome

Answer 8

CGG repeats in the 5’ region of the FMR1 gene–> methylation of the cytosine residues in the CpG islands–> FMR1 inactivation— normal males have 6-50 CGG repeats here but affected males have >200 copies of this which leads to increased transcriptional silencing

Question 9

two classes on transcriptional activators and repressors

Answer 9

1. sequence specific DNA binding proteins and 2. cofactors

Question 10

sequence specific DNA binding proteins

Answer 10

bind to sequences that are 6-8 bp long and bind DNA by inserting alpha helices into DNAs major groove–> amino acid side chains of protein interact with the bases in DNA

Question 11

2 domains of sequence specific DNA binding proteins

Answer 11

1. DNA binding domain (highly structured and conserved) and 2. activation or repression domain (not conserved, unstructured, bind cofactors or GTFs)

Question 12

4 families of sequence specific DNA binding proteins

Answer 12

homeodomain proteins, zinc finger proteins, basic leucine zipper (bZIP) and basic helix loop helix (bHLH)

Question 13

craniosynostosis

Answer 13

premature closure of 1+ sutures in the skull, boston type occurs because of a mutation in the MSX2 homeodoman protein– normally this protein affects transcription and helps develop the face but if you mutate this homeodomain with 1 amino acid substitution then it binds DNA too strongly and you get a gain-of-function allele that increases transcription so the cranial closure occurs too soon

Question 14

androgen insensitivity syndrom (AAIS)

Answer 14

males have a normal karyotype but have a mutation in the DNA binding domain or ligand binding domain of the androgen receptor (thats a zinc finger DNA binding protein) so patents are thus less responsive to androgens

Question 15

Waardenburg syndrome type II

Answer 15

mutations in a microphtalmia associated transcription factor (MITF) gene that encodes for a bHLH DNA binding protein, 15-20% of patients have a mutation that encodes a transcription factor that is important in melanocyte development

Question 16

what do cofactors bind

Answer 16

NOT DNA but instead sequence specific DNA binding proteins

Question 17

what is combinatorial control

Answer 17

because sequence specific DNA binding factors usually bind as homodimers and heterodimers, the monomers usually differ in binding specificity and you can form different heterodimers that then can increase the number of potential binding sequences

Question 18

what parts of histones can get modified and why

Answer 18

the N termini has a lot of lysine’s that can be modified through acetylation, phosphorylation, methylation and ubiquitination

Question 19

2 classes of chromatin remodeling factors

Answer 19

1. dna dependent ATPases (SWI/SNF) 2. Factors that reversibly modify histones through acetylation (HATS and HDACS)

Question 20

how do DNA dependent ATPases work

Answer 20

ust ATP hydrolysis to move histones along dna

Question 21

what are HATS

Answer 21

histone acetyltransferases, acetylate N termini of histones, allow TFs to bind, COACTIVATORS

Question 22

what are HDACs

Answer 22

histone deacetylases remove acetyl groups from the N termini of histones, COREPRESSORS

Question 23

what are transacting factors

Answer 23

can be activators or repressors because they can recruit either hats or hdacs

Question 24

example of trans acting factor

Answer 24

thyroid hormone receptor

Question 25

rubenstein taybi syndrome

Answer 25

mutation in 1 copy of CREB binding protein (called CBP), normally CBP is a transcriptional coavtivator for genes and it is a HAT but mutate one of them–> fewer activators–> lots of transcriptional changes

Question 26

leukemia

Answer 26

usually because of chromosomal translocations, often involves fusing transcriptional regulators with HATs or HDACs

Question 27

two main ways that transcriptional activators and repressors work

Answer 27

1. interact with GTFs/polII associated proteins to affect initiation or elongation, 2. interact with chromatin