Gene Regulation I Flashcards
How does positive regulation make more sense in highly differentiated cell systems?
Most genes are off until needed making fine control easier in huge genomes like ours.
What happens to most eukaryotic genes?
They are silenced
Why is heterochromatin not transcribed?
This is because the DNA is hyper methylated at CpG nucleotides and their histones are deacylated
Why is euchromatin transcribed?
It’s DNA is hypomethylated and it’s histones are acylated
How are histones modified when being transcribed?
Histone acetyl transferases (HATs) unwind DNA to promote transcription Histone deacetylases (HDACs) reverse the process to form nucleosomes
What happens to chromatin overall when being transcribed?
Chromatin relaxes, resulting in hypersensitivity to DNase treatment
What is DNase treatment?
CpG islands
Hpall Tiny Fragments or HTF islands
What does PCAF do?
It’s a HATs
Acetylates residues in H3 and H4
What does NuA4 do?
Acetylates H2A and H4
What does SWI/SNF do?
Nucleosome movement; transcriptional activation
What does the ISWI family do?
Nucleosome movement; transcriptional repression
What does epigenetic refer to?
Changes in phenotype without changes in genotype “heterochromatin vs euchromatin”
What does DNA methylation do?
Gene silencing
What does histone acetylation do?
Gene activation
What are CpG’s considered to be?
Hotspots for genetic mutation
What do methylcytosines attract?
Repressor proteins
How to methylcytosines attract repressor proteins?
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
What regulates X-inactivation?
By the Xist gene transcript, transcribed from inactivated X chromosome
What is the Xist gene?
A large (17kb) polyadenylated transcript with no large ORF… No protein product
What happens to Xist once the X chromosome is inactivated?
Xist remains in nucleus & associates with inactivated X
What makes deletion in region 15q11-13 different than others?
The genes are differentially silenced in male and female gametes
What is Angelman syndrome?
Only paternal genes are expressed meaning there was a mutant maternal chromosome 15
What is Prader-Willi syndrome?
Only maternal genes are expressed meaning there was a mutant paternal chromosome 15
What are the symptoms of Prader-Willi syndrome?
Mental retardation Obesity Hypogonadism Small hands & feet Itchy skin Voracious appetite
What are the symptoms of Angelman Syndrome?
Mental retardation Hypotonia Absence of speech Large mandible Tongue thrusting Epilepsy
What does folate deficiency affect during development?
Increases risk for neural tube defects
What does hyperhomocysteinuria increase risk for?
Increases risk for cardiovascular disease
What are some epigenetic changes that cigarette smoke causes?
Hypomethylation of oncogenes
Hypermethylation of tumor suppressor genes
What are the two basic classes of genes?
Constitutive - essential for cell survival
Inducible/repressible - highly regulated
What are transcription factors?
DNA binding proteins that regulate transcription initiation
What do transcription factors do?
Recruiter for basal transcription machinery
Enhance speed and efficiency of RNA polymerase
How much can transcription factors increase the transcription rate by?
By many thousand full
What are basal factors? And what are some examples of them?
A transcription factor that positions RNA polymerase on the core promoter
TFIID,A,B,E,F,&H
What are activators?
Transcription factors that bind to enhancer elements; up rate of assembly of transcriptional machinery
What are mediators?
Adapter molecules that connect activators (&repressors) to basal factors
What are repressors?
Transcription factors that bind to silencer elements; interfere with activators to slow transcription or induce heterochromatin formation
What are 3 heterochromatin modifiers?
HATs, HDACs, HMG proteins
