Flashcards in Gene Expression Shred Fest I LO Deck (47)
what determines the amount of protein within each cell? (4)
1. amount of mRNA
2. frequency of mRNA translation
3. stability of the protein
4. Rate of degradation of protein
what is the most important mechanism for determining gene expression and amount of protein synthesized?
what are the 2 basic components important to eukaryotic gene expression?
1. DNA control elements-part of DNA that acts locally (cis)
2. transcriptional activators/repressors that act on other genes to regulate their transcription (trans)
where do DNA control elements act?
locally, transcription factors bind to elements that control expression of that gene
what are the 3 DNA control elements?
1. TATA box/initiator (promoter)
2. promoter proximal element
what is the TATA box?
located 25-35 bp upstream of transcription start, determines site of transcription initiation and directs binding of RNA pol II
what is the promoter proximal element?
200 bps upstream of start site and about 20 bps long, helps regulate transcription
what is the enhancer?
200-tens of thousands bps upstream or downstream from promoter or within an intron
what binds at the TATA box?
general transcription factors like TATA binding protein
what are the 3 diseases associated with mutations in the DNA control elements?
2. Hemophilia B-Leyden
3. Fragile X-Syndrome
what does an enhancer do?
binding of proteins enhances transcription levels
what is a silencer?
Section of DNA that binds transcription regulating factors called repressors
how does a silencer work?
when repressors bind, RNA polymerase is prevented from initiating transcription, thus lowers or eliminates transcription
how is thalassemias inherited?
what is thalassemias?
blood disease that occurs due to different genetic mutations such as mutation or deletion
what mutation causes B-Thalessemias?
B-globin promoter mutation causing decreased transcription of this protein but not complete loss of this protein
what mutation causes yDB thalessemias?
deletion of locus control region (LCR) of B-globin gene cluster, very severe form because LCR directly regulate expression of all genes in that cluster
what chromosome is hemophilia B leyden linked to?
what does hemophilia B leyden affect?
how does hemophilia B leyden affect males?
have 1% of normal factor IX active until puberty, once androgen receptor becomes active, produce about 60% of normal factor IX
what is the presentation of fragile X syndrome?
mental retardation, dysmorphic facial features, postpubertal macroorchidism (abnormally large testes)
why does fragile-X syndrome develop?
expansion of CGG trinucleotide repeats in the 5' region of FMR1 gene on X chromosome. normal humans have about 6-55 repeats but fragile X syndrome patient have between 230-4000 repeats
why does increasing the amount of CGG repeats cause fragile X syndrome?
there is an increase in the methylation of cytosine residues in CpG islands of FMR1 promoter, methylation then causes silencing of FMR1 gene
what is the severity of fragile X syndrome directly related to?
the number of CGG repeats
what does the mutation in hemophelia B leyden disease prevent?
binding of appropriate transcriptional activators to Factor IX gene
what are transcriptional factors?
proteins encoded by one gene that act on other genes to regulate their transcription (activators and repressors)
what are the 2 classes of activators and repressors?
1. sequence-specific DNA binding proteins
what is a sequence-specific DNA binding protein?
protein that binds to the promoter or enhancer elements in their target genes to regulate transcription
how do sequence-specific DNA binding protein binds to the DNA?
insert alpha helices into the major groove of DNA