Epigenetics 1 Flashcards
What is chromatin?
DNA and proteins that make up nucleus contents
What are the cues that cause the epigenetic alteration of chromatin?
Developmental cues - differential gene expression in development
Environmental cues - differential gene expression through adult life
What are the 3 main types of epigenetic modifications?
DNA methylation
Histone modifications - e.g. aceylation, phosphorylation
microRNA (miRNA)
How can DNA methylation be determined and how is this used?
Bisulphite treatment - bisulphite conversion of C to U if not methylated - does not convert if methylated
Sequencing
What is the effect of methylation?
Chromatin compaction - transcription machinery cannot access promoter - gene silenced
What type of enzyme methylates DNA?
Methyltransferases
How can histone modifications be determined and how is this used?
Chromatin immunoprecipitation (ChIP) - link DNA to proteins - cut into short pieces - antibodies for specific modification at certain residue on histone recognise protein - identify linked DNA fragment by sequencing - determine gene from sequence library
What type of enzyme removes acetyl groups from histone tails?
Histone deacetylases (HDACs)
What is the effect of histone acetylation?
Chromatin relaxation - transcription machinery can access promoter - gene expressed
What are the roles of miRNAs?
Target mRNA for degradation - prevent synthesis of certain proteins
Can bind enzymes of epigenetic modifications - send for degradation
Can bind DNA - reorganise chromatin - alter relaxation/compaction
What environmental cues influence the epigenome?
Toxin exposure
Stress
Diet
Physical activity
Which genes have altered methylation in ASD, how is this changed, and what are their roles?
Increased methylation
Oxytocin receptor (OXTR)
Glutamate decarboxylase 1 (GAD1) - catalyses GABA production
Engrailed-2 (EN2) - controls pattern formation in neurodevelopment
Reelin (RELN) - neuronal migration in development, modulates adult synaptic plasticity
MeCP2
Which differentially methylated gene pathways have been linked to ASD by EWAS?
Neurodevelopment
Immune and inflammatory response
Which types of epigenetic alterations are linked to psychotic diseases (bipolar disorder, schizophrenia)?
DNA methylation
Histone modifications
miRNA dysregulation
Which gene has altered histone acetylation in SCZ, how is this changed, and what is its role?
Decreased acetylation
GAD1 - catalyses GABA production
Which epigenome-regulating gene has been linked to SCZ and how?
HDAC1
Increased expression in SCZ frontal cortex
Which long-used drug for bipolar disorder (and schizophrenia) affects epigenetic mechanisms and how?
Valproate
Non-specific HDAC inhibitor - increases histone acetylation
