Gene Expression Flashcards
TATA box/initiator sequence
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
promoter proximal sequence
200 bp upstream of transcription site, roughly 20 bp long, can be bound by factors in a cell type specific manner
enhancers
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
transcription factor
protein that binds DNA to regulate what gets transcribed by recruiting or blocking RNA polymerase, can also alter chromatin structures
Thalassemias beta
inherited anemia because erythroid cells don’t produce the beta-globin promoter which causes less beta-globin mRNA so less protein gets made
thalassemias gamma delta beta
deletion of the locus control region (LCR) of the beta globin gene cluster
hemophilia b leyden
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
fragile x syndrome
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
two classes on transcriptional activators and repressors
- sequence specific DNA binding proteins and 2. cofactors
sequence specific DNA binding proteins
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
2 domains of sequence specific DNA binding proteins
- DNA binding domain (highly structured and conserved) and 2. activation or repression domain (not conserved, unstructured, bind cofactors or GTFs)
4 families of sequence specific DNA binding proteins
homeodomain proteins, zinc finger proteins, basic leucine zipper (bZIP) and basic helix loop helix (bHLH)
craniosynostosis
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
androgen insensitivity syndrom (AAIS)
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
Waardenburg syndrome type II
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
what do cofactors bind
NOT DNA but instead sequence specific DNA binding proteins
what is combinatorial control
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
what parts of histones can get modified and why
the N termini has a lot of lysine’s that can be modified through acetylation, phosphorylation, methylation and ubiquitination
2 classes of chromatin remodeling factors
- dna dependent ATPases (SWI/SNF) 2. Factors that reversibly modify histones through acetylation (HATS and HDACS)
how do DNA dependent ATPases work
ust ATP hydrolysis to move histones along dna
what are HATS
histone acetyltransferases, acetylate N termini of histones, allow TFs to bind, COACTIVATORS
what are HDACs
histone deacetylases remove acetyl groups from the N termini of histones, COREPRESSORS
what are transacting factors
can be activators or repressors because they can recruit either hats or hdacs
example of trans acting factor
thyroid hormone receptor
rubenstein taybi syndrome
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
leukemia
usually because of chromosomal translocations, often involves fusing transcriptional regulators with HATs or HDACs
two main ways that transcriptional activators and repressors work
- interact with GTFs/polII associated proteins to affect initiation or elongation, 2. interact with chromatin
