Regulation of Gene expression Flashcards
Regulation of gene expression occurs at what stage?
1) chromatin structure
2) transcription initiation
3) transcript processing
4) mRNA stability
*regulation occurs at each step*
What is a constitutive gene?
What is an inducible gene?
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
What determines which genes are expressed?
availability/accessibility of gene within the chromosome
availability of proteins that promote transcription (transcription factors)
are histones positively or negatively charged?
histones are positively charged
DNA is negatively charged
so DNA and histones have ionic attractions
histone tails are rich in what residue?
Lysine residues
if the chromatin is acetylated, whtat does that mean?
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
What are HDACs?
they are repressors- HDACs
when we inhibit HDAC, what happens?
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
What are the 3 general regions of a gene?
- promoter region - transcriptional start site
- coding region - eukaryotes- introns and exons
- 3’ UTR- important for mRNA stability and determines half life of mRNA
what is the promoter region of a gene? what types of promoters are there?
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
What are the two different types of basal elements?
- 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
What are transcription factors?
Transcription factors are proteins that bind specific DNA sequences - they recognize the response/enhancer element -they control the rate of transcription
what must the transciption factor bind to ‘turn on’ the transcription of the gene?
the transcription factor must bind to promoter/ enhancer
how is the transactivation domain usually regulated?
the TAD is usually regulated by phosphorylation of specific residues of TAD
what regulates the rate of transcription of a gene?
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
what part of mRNA encode the protein coding region of the gene mRNA?
the exons
What are the main areas of post-transcriptional regulation?
- mRNA stability
- differential mRNA splicing
what determines mRNA stability?
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
what do you cal the process of rearranging/cutting out exons/introns?
splicing and exon shuffling
what are miRNAs?
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
