Epigenetics Flashcards
what is epigenetics and what does it affect
gene expression states that are stable over rounds of cell division but do not involve changes in the underlying DNA sequence of the organism
developmental potential and multicellular identity
nuclear architecture
transcriptional silencing of repetitive sequences
What cells fit the following descriptions and what are its epigenetic status: totipotent, pluripotent, multipotent, unipotent
Totipotent=zygote global DNA demethylation
Pluripotent=IPS cells etc. only active X chromosomes, global repression of differentiation genes by polycomb proteins, promoter hypomethylation
multipotent=adult stem cells X inactivation, repression of lineage-specific genes by polycomb proteins, promoter hypermethylation
Unipotent=differentiated cell types X inactivation, derepression of polycomb silenced lineage genes, promoter hypermethylation
what does methyation do to expression
represses expression of genes
what kind of epigenetic modifications influence how the DNA is packaged into chromosomes and regulate genome function
sites of attachment, loops and long range interactions
compaction, accessibility of DNA in chromatin
modification of core histones at N-termini
Methylation of DNA at CG dinucleotides
What helps methylation and what helps demethylation
Methylation=methyltransferase
demethylation=TET proteins
what types off methyltransferases are there and what do they do
Dnmt1-maintenacne methylation of hemi-methylated strands
Dnmt2-tRNA methylase
Dnmt3a&b-de novo methylation (methylation of unmodified DNA during development)
Dnmt3L-oocyte and sperm specific roles. Required to establish imprinting in oocyte
What are the two types of methylation-mediated transcriptional repression
Direct inhibition-methylation prevents transcription factor action on promoter->gene not transcribed
Indirect inhibition-repressive chromatin shuts down preventing other factors from coming in and maake the gene active in this region
What does the post translational modification of N terminal tails affect
active/silent genes, promoters, enhancers, transcriptional elongation, replication
what can the histone code be used for and give examples
predicting regulatory regions
H3k9me3/H3k20me3-heterochromatin and imprinting control regions=parasitic DNA
H3k27me3-polycomb binding, devvelopmentally regulated promoters and enhancers
H3k4me3-active promoters
H3k4me1/H3k27me1-enhancers/regulatory sequences
H3k36me3/H3kxAc-active transportation
What doe ENCODE do
shows how different histone marks are in particular region compared to healthy
identification of non traditional diseases causing mutation
identification of long range enhancer mutations and other forms of GWAS
what could epigenetic defects cause
cancer, silver Russel syndrome, beckwith wiedermann syndrome, transient neonatal diabetes mellitus, heart disease, autoimmune disease, neurogical+psychiatric
what is used for he study of epigenetic control of genome function
chromosome architecture (heterochromatin), silencing of retrotransponons/parasitic elements, sex chromossome dosage compensation, alellic exclusion, environmentally induced strategies in expression, developmental reprogramming, genomic imprinting
What happens when genomic imprinting goes wrong
parthenogenote-death because placenta not developed (only maternal)
androgenote-death because embryo doesn’t develop (only paternal)
What is genomic imprinting
epigenetic marks are set in the germline, maintained during development and are reversible for re-setting in the next generation
manifests as non Mendelian inheritance, involved in human disease
Why could genomic imprinting pose a threat
if gene is maternally/paternally silenced, greater risk of having no working copies
What is genomic imprinting involved with
development and growth of embryo and extra embryonic tissues, birth defects and cancer, reproductive technologies that involve cloning
What are the types of uniparental disomies and why could it pose a problem
paternal, maternal, partial duplication (translocation of chromosome, right no. chromosomes but small portion at top could be uniparental)
most genes are expressed from both alleles but imprinted genes may only be expressed from one parent so misexpresssed in UPD
Give examples of human imprinted genetic disease
prader-willi syndrome angelman's syndrome beckwith-wwiedeman ssyndrome silvver-russel syndrome albright hereditary osteodystrophy transient neonatal diabetes
What is the difference between prader-wiilli syndrome and angeelman syndrome
Both involve cytogenic deletion of 15q11
PWS-deletion from father, mother asymptomatic, also uniparental disomy of CHr15 (no father=same effect as mutation and deletion). involves loss of function of multiple paternally expressed genes
AS- deletion from mother, father asymptomatic. Associated with mutation of single imprinted gene UBE3A
How do the symptoms of Angelman and Prader-willi differ
Angelman-happy disposiition, inappropriate laughter, widely spaced teeth, wide mouth, stiff uphed armss and broad stance, mental retardation
prader-willi-central obesity, short stature, small hands and feet, mild facial dysmorphism, always hungry
what does a good diagnostic test for AS and PWS do
Methylation status at the AS/PWS region is diagnosed by 2 methylation-PCR methods for AS and PWS
Methylation identifies patients with a deletion, UPD or imprinting mutation
What are common symptoms for Beckwith-Wiedemann syndrome
large tongue, large organs, large body size, hernia of navel, small head, cancer predisposition
What is BWS caused by
deregulation of imprinted genes
most cases are sporadic and reult from epimutation at either of the two 11p15.5 imprinting centres (IC1 and IC2)
germline mutations in NLRP2 gene in a familial form of this imprinting disorder
What elevates BWS incidence
IVF
silver-russel syndrome featuresd
low birth weight, decreased birth length, triangular shaped face, postnatal growth retardation, poor apetitie/reflux, fifth finger clinodactyly, normal head size appearing large because of reduced body length and weight
SRS cause
7 sporadic cases have maternal UPD 7. Paternal UPD 7 are normal. SRS exhibits imprinting effect
albright’s hereditary osteodystrophy causse
associated with imprinted GNAS locus
albright’s hereditary osteodystrophy symptoms
abnormality in end organ (rrenal) response to parathyroid hormone though parathyroid glands itself are normal. Short metacarpals, metatarsalss, phalanges, wide bone, thickening of calvaria.
