Chromatin and Epigenetics

Question 1

describe position dependent expression of genes

Answer 1

position in the genomes where large heterochromatin blocks are established and maintained

SILENCERS

genes close to silencers are strongly repressed

repression of the genes depends on their position relative to the silencer –> does NOT depend on their promoters

Question 2

describe the mating type loci in yeast

Answer 2

HML and HMR are constantly repressed
genetic studies identified proteins that regulate this repression
Rap1 binds next to the repressed loci and recruits Sir (silent information region) proteins

Question 3

what do sir proteins do?

Answer 3

spread away and cover the chromatin of nearby genes
Sir2 is a HISTONE DEACETYLASE –> deaxetylases the histones within HML and HMR
deacetylated histones bind tighter to DNA and form heterochromatin
If the genes in HML and HMR are moved away from HML and HMR loci, they become active

Question 4

what is necessary for positional gene repression?

Answer 4

histone hypo-acetylation

Question 5

describe lysine –> arginine substitution in histones

Answer 5

Lysine –> Arginine substitutions in histone tails
arginine retains positive charge, cannot be acetylated
DNA-histone interaction is strong, chromatin is compact, gene repression cannot be reversed
mutants maintain permanent gene repression at telomeres

Question 6

describe the lysine –> glutamine substitution in histones

Answer 6

glutamine has a neutral charge, resembles acetylated lysine, cannot be deacetylated to gain a positive charge
chromatin is decondensed, gene cannot be repressed
maintain permanent gene activation at telomeres

Question 7

describe the conclusions of histone acylation

Answer 7

acetylation –> reduced positive charge, allows for opening of chromatin (euchromatin) and for transcription

deacetylation –> reconstitutes positive charge, strengthens DNA-histone interactions, compacts chromatin, suppresses transcription

Question 8

give an overview of gene silencing at the telomeres of S. cerevisiae

Answer 8

same proteins regulate silencing at the telomeres
Rap1 binds directly to the telomeric repeatsSir proteins spread in the sub-telomeric regions and cover them with condensed hypoacetylated nucleosomes
many telomeres cluster at the periphery of the nucleus and form large 3D heterochromatin blocks

Question 9

describe the steps of gene silencing at the telomers

Answer 9

Sir2, Sir3, Sir4 proteins attach onto N-term ends of histone
nucleosomes condense and multiple telomeres associate