Lecture 4 - epigenetics Flashcards
Nucleosome
DNA wrapped around histone proteins
Chromatosome
Nucleosome + H1 histone linker protein
Chromatin fibres
Folded up chromatosomes
Chromosomes
Coiled Chromatin fibres
Chromosome are packaged in NUCLEUS
Epigenetics are…
Biochemical markers placed on top of DNA to control which genes are switched on/off
* Can be reversed
DNA methylation
Methyl group added directly to cytosine residue that exists in a CpG sequence
H3K9 acetylation
H3K9 added to histone tail
* Transcription activation
* Active chromatin
H3K27 trimethylation
H3K27 added to histone tail
* Transcription repression
* Repressed chromatin
What enzymes are responsible for the additon of methyl groups to cytosine residues?
DNA methyltransferases.
CpG sites
Cytosine site followed by a guanine nucleotide
CpG islands
High density of CpG sites
* often near gene promoters
Methylation in promoter regions is associated with…
Gene silencing
How does methylation of CpG sites cause gene silencing?
Closes the chromatin structure (Tighter, more coiled)
* DNA polymerase CANNOT access and therefore cannot transcribe
“HAT”
Histone acetyltransferase
* OPENS THE CHROMATIN (opposite to methylation for the most part, there are exceptions)
“HDAC”
Histone deacetylase
* CLOSE CHROMATIN
Methylation in development
- TET - responsible for demethylation in development
- DNMT3a/b - responsible for denovo remethylation
- DNMT1 - maintenance methylation
What are the main Neurodevelopmental and neuropsychiatric disorders?
- ASD
- ADHD
- Tics
- OCD
What % of NDDs are caused by gene and environment?
Causes 90%
* 1000s of vulnerability genes (DNA)
* Epigenetic modifications
* Environmental risk factors
How is the immune system related to NDDs?
- Elevated pro-inflammatory cytokines
- Dysregulated peripheral immune signalling
- Dysregulated microglia activity
- Increased comorbid immune-related conditions
Maternal immune activation hypothesis
Immunological activation of the mother during pregnancy in combination with genetic predisposition leads to NDD
What causes Rhett syndrome?
Random mutation in the MECP2 gene on the X chromosome
Who is effected by Rhett’s and what are the symptoms?
Majority female (fatal in males)
* Loss of motor skills, language
* Breathing irregularities
* Seizures
* Slow growth
* Abnormal muscle tone
* Autism-like symptoms
What causes Kabuki syndrome?
Random mutation in the KMT2D gene (Somatic)
What are the symptoms of Kabuki?
- Distinctive facial features
- Growth delays
- musculoskeletal abnormalities
- cardiac problems
- intellectual disability
What is occuring at a cellular level in Kabuki?
Too much closed chromatin
(Unbalanced methylation)
Transcriptomics
Set of all RNA transcripts in a population of cells (coding and non-coding)
Identify some applications of transcriptiomics
- Identify genes + pathways that respond to environmental stress
- Disease diagnosis + profiling (cancer)
- Uncover function of specific genes
- Quantifying gene expression changes (drug targets)
- Drug repurposing
