T3A2 Flashcards
(31 cards)
Short term responses in the target cell
modify immediate cell processes, (i.e. metabolism,
movement) Can include post- translational protein
modifications
Long term responses in the target cell
Modification of gene expression and/or
development
Genome is
inherited
Epigenome can be
altered
Chemical DNA modifications that occur along the genome
change gene activity without altering the DNA
sequence
Epigenetic processes are essential for
normal development, cell differentiation, and are increasingly being recognized as being involved in human diseases
Epigenetic mechanisms
- Modifications of histone tails (Alters wrapping of DNA around histones)
- DNA methylation (alters ability of transcription factors and RNA polymerase to interact with promoter)
- Overall result: Chromatin remodeling
Epigenomics
studying the epigenetic modifications across an individual’s entire genome and relate them to cell
function and even disease
Cancer cells abnormal genomes
lower levels of methylation, increase expression of genes that promote cell growth or higher levels of methylation decrease expression of genes that keep cell growth in check or repair DNA or initiate cell death
Cancer can begin when
mutations change a cell’s DNA sequence, abnormal epigenomes, expression of some genes are turned up and some are turned down – often in the very same cells
Agouti gene encodes
protein that signals to melanocytes to switch from producing black to yellow pigment
Agouti yellow mice have insertion in
Agouti gene, making them obese and yellow, and pre-disposed to diabetes, and cancer
In normal healthy mice (brown), the agouti genes are
kept off due to DNA methylation
In genetically identical obese sibling (yellow), the same
genes are
not methylated…leads to yellow colour… also,
predisposition to cancer and diabetes
Nutrients
silence the Agouti gene but do not alter the gene sequence
What alters coat colouration and disease
susceptibility?
Maternal dietary supplementation of Agouti mice with methyl donors (i.e. folic acid, choline, vitamin B12)
Genetically identical littermates can range in colour across a spectrum of yellow to mottled to brown mice due to
epigenetic variations established in the
womb
Identical twins
- Identical or monozygotic twins =1/250 live births
- A single fertilized egg divides into two separate embryos
- Identical twins inherit the exact same genes from their parents
Adding B12, folic acid, methyl sources helps closure of spinal cord leading to
Decrease in spina bifida and neural tube deficiences
noticeable differences in facial aging in twins can be caused by
smoking history, environmental cues with aging causing changes in gene expression
Monozygotic twins share
common genetic blueprint, but have different phenotypes that can be influenced by epigenetic modifications
Study done in spain
Set out a call for monozygotic twin pairs, young and old, look at level of epigenetic differences old vs young
Study method
- 40 volunteer Caucasian twin pairs from Spain
- Age range: 3-74 years of age
- Profiled epigenetic patterns of DNA methylation, & histone protein acetylation. Microarray analyses
Mapping of chromosomal regions for DNA methylation
reveals
differential methylation in twin pairs
