epigenetics Flashcards
define epigenetics
all the processes that lead to heritable changes in gene expression as cells divide
is the genome static or flexible?
static
is the epigenome static or flexible?
flexible
what is the barker hypothesis?
the environment that a fetus faces in utero affects their risk of developing disorders in later life
what are the 4 types of epigenetic mechanisms?
DNA methylation
micro and small RNAs
chromatin architecture
histone modification
does DNA methylation activate or inactive a gene?
inactivates it
explain the process of DNA methylation
methyl group adds to cytosines immediately adjacent to guanines (e.g. CpG islands in promoter regions) using DNA methyltransferase
how does DNA methylation cause gene silencing?
methyl group stops RNA polymerase II from binding
stops transcription factors from binding to the promoter region
what are CpG islands?
areas rich in C and G in the promoter region
how do micro and small RNAs cause gene silencing?
miRNA binds to complementary regions on the DNA so ribosomes cant attach and translate
can induce degradation of mRNA
what changes in the shape of the histone can take place?
sliding
ejection
H2A-H2B dimer ejection or replacement
what are the main types of post-transcriptional histone modifications?
acetylation
methylation
phosphorylation
ubiquitination
what amino acid does modifications of histones occur on?
lysine
what does histone acetylase do?
catalyses the transfer of acetyl group onto lysine
how does acetylation affect a histone?
makes the promoter more accessible for transcription
what does histone deactylase do?
reverses the process of adding an acetyl group on
how does hypomethylation play a role in the development of cancer?
less methylation
less silencing
more room for tumours to form
what is imprinting?
the preferential expression of either the paternal or maternal allele
name imprinting related disorders and how they’re caused
part of chromosome 15 deleted
Prader-Willi - allele from father
Angelman - allele from mother
define genome
The complete set of genes / genetic material present in a cell or organism
define epigenome
the parts of the genome that are actually used
what does low availability of nutrients in prenatal stage followed by improvement in nutritional availability in childhood cause?
metabolic disorders e.g. diabetes type 2, obesity, coronary heart disease
what is a nucleosome?
DNA wrapped around a histone
how does DNA packing prevent gene expression?
prevents transcription proteins from accessing DNA
how does chromatin architecture affect DNA expression?
- Alter the contact between DNA and histones
- Alter the path of the DNA as it winds around the histones
- Alter the structure of the nucleosome core itself
what does histone acetylation do?
opens chromatin
DNA accessible
transcription activated
what does histone deactylation do?
closed chromatin
DNA inaccessible
transcription repressed
what are HDAC inhibitors?
used to increase gene transcription for some genetic conditions
what does genome wide hypomethylation occur with?
ageing and tumourgenesis
what is non-coding RNAs?
functional RNA but not translated into proteins
what causes Prader Willi syndrome? how does it present?
deletion of PATERNAL copy of chromosome 15q11 q13
leads to language, motor and developmental delays, excessive weight gain
what causes Angelman syndrome? how does it present?
deletion of MATERNAL copy of chromosome 15q11q13
severe mental retardation, happy demeanor, non-verbal
what are epigenetic therapies?
HDAC inhibitors
DNMT inhibitors
Non-coding RNA
Osteopathic manipulation
how does reducing calorie lead to increased lifespan?
works by maintaining degree of methylation
