CPPS403 - Epigenetics - 7 Flashcards
(16 cards)
What is the role of TBX5 in Holt-Oram syndrome?
TBX5 is a transcription factor expressed in the heart and developing forelimb
Mutations in TBX5 lead to congenital heart defects (CHDs) and Holt-Oram syndrome.
What type of mutation was identified in TBX5 cis-regulatory elements?
A candidate single point mutation that destroys cardiac expression properties of the enhancer
This mutation was found in patients with isolated CHDs not diagnosed with Holt-Oram syndrome.
What are DNMT3A, 3B, and 3L?
De novo methyltransferases that can methylate any CG dinucleotide
They play a role in establishing DNA methylation patterns.
What is the function of DNMT1?
Maintains existing DNA methylation patterns and methylates the nascent DNA strand
DNMT1 methylates only CG dinucleotides paired with a methylated CG on the opposing parental DNA strand.
What occurs to primordial germ cells as they reach the genital ridge?
Their genomes are progressively demethylated
This process is part of epigenetic reprogramming.
What is genomic imprinting?
Silencing of one allele according to the parent of origin
It results in monoallelic expression and occurs during gametogenesis.
What is the significance of imprinting control regions (ICRs)?
They regulate the expression of imprinted genes based on parental origin
Examples include ICR1 and ICR2 which are involved in disorders like Beckwith-Wiedemann syndrome.
What is the effect of hypomethylation on ICR1?
It activates ICR1, allowing H19 to be expressed and preventing IGF2 expression
This is important for the regulation of growth factors and non-coding RNAs.
What is uniparental disomy?
A condition where both copies of a chromosome originate from one parent
It can lead to monoallelic expression and is often a result of nondisjunction.
What is X-chromosome inactivation?
A gene dosage compensation mechanism in females that equalizes X chromosome expression
It results in one X chromosome being randomly inactivated and forming a Barr body.
What role does Xist play in X-chromosome inactivation?
Xist spreads along the future inactive X and induces conversion to a heterochromatic state
It acts as a scaffold for repressive factors.
Fill in the blank: Mutations in TBX5 lead to _______.
congenital heart defects (CHDs)
True or False: Imprinting disorders are reversible.
True
Imprinting can be re-established depending on the sex of the parent.
What are long non-coding RNAs (lncRNAs)?
Regulators that can modulate transcription through epigenetic modifications
They may recruit chromatin-remodeling complexes to specific loci.
What is the phenotype of Silver-Russell syndrome commonly caused by?
Hypomethylation of ICR1 on both chromosome 11s
This results in silencing of both IGF alleles.
What happens during the wave of genome re-methylation after fertilization?
It coincides with the differentiation of cell lineages
This process is crucial for establishing somatic cell DNA methylation patterns.
