Epigenetics Flashcards
DNA modifications
What is Epigenetics?
-It is the study of alterations in gene expression(phenotype) caused by changes other than changes in DNA sequence
-It occurs either via DNA modifications or chromatin modifications
What is DNA methylation
-It is the conversion of cytosine to methylcytosine by adding a methyl group
-Methylation only occurs on CpG islands: where cytosine occurs next to guanine
-always say that methylation occurs on 5’-CG-3’
-complementray cytosine will also be methylated
what enzyme is responsible for methylation?
DNA methyltransferase
How does repression of transcription work?
Due to DNA methylation
-DNA methylation can sterically hinder (block binding sites) of TF to gene promoters( methyl groups block binding sites)
-TF can recruit methyl CpG binding domain proteins (MeCP) to methylated DNA via a methyl CpG binding domain (MBD) in order to further suppress gene expression
-DNA methyl transferase proteins can also recruit histone deacetylases to from a tightly packed chromatin structure
Histone deacetylases an also be activated by MeCP to cause loosely packed chromatin to condese into a tightly packaged chromatin structure
what does DNA methylation do?
It silences gene expression by either:
-directly repressing transcription
-Aiding the formation of repressive chromatin structures( beads on a string to tightly compacted chromatin)
Where can DNA methylation arise from?
-De novo DNA methylation occurs during early development
-Inherited DNA methylation patterns
Note: methylation is a completely reversible process as its main function is to regulate the amount of protein synthesised
What type of histone modifications can occur?
-Acetylation
-methylation
-Phosphrylation
What does DNA methylation also contribute to?
Besides repression of transcription
-Genomic imprinting: This mark of methylation allows somatic cells to remember which parent a gene was inherited from. ( The IGF2 gene must be silenced from the maternal gene otherwise it will cause a genetic disease)
-X-Inactivation: In females, every cell has to express genes only from one x-chromosome and the other one must be inactivated. This is to ensure that the dosage of proteins produced is the same in males and females.
what is acetylation
-Addition of an acetyl group by histone acetyltransferase (HATs)
-acetylation occurs on lysine groups of histone tails
-Results in a reduction in net positive charge so that DNA disassociates fro, histone tails so that transcription can more easily occur.
-It also recruits bromodomain containing chromatin remodeling complexes which areprotein complexes that recognise acetyl groups and move around DNA and proteins so that there is space for RNA pol to bind to DNA
what is De-Acetylation?
-Histone de-acetylases (HDACs) remove acetyl groups so that DNA reassociates with histones in order to result in gene repression
-It is recruited by factors involved in repressing transcription like DNMTS
Note: high levels of deacetylation are associated with high levels of methylation =less transcription
What is histone methylation
-Addition of a methyl group onto lysine and arginine
-enzyme=Histone methyltransferase
-It does not reduce net positive charge of histones
-Attracts chromodomain-containing chromatin remodeling complexes/proteins
what are chromayin remodeling complexes
-They are attracted by regulatory/activator proteins
-Bromodomain: Attracted to acetylated residues and open chromatin to increase gene expression
-Chromodomain: Attracted to methylated residues and they close chromatin.
what is the SWI/SNF complex
It disrupts histone/DNA contact and releases histones
what is ISWI/NURF (nucleosome remodeling factor)?
They cause nucleosome sliding which is important for exposing binding sites for transcription factors and RNA Pol to bind to
Give examples of environments that can modify the epigenome?
-Abestos exposure
-Traffic pollution
-BPA
-Alcohol
