4 Epigenetics Flashcards
(18 cards)
Euchromatin
Transcription occurs
ACTIVE
Less tightly wound
Heterochromatin
Tightly wound - NO DNA transcription
Genes are silenced
Most prevalent in cells less active or not active at all
Open chromatin —> condensed chromatin
DNA methylation
His tone deacetylation
Condensed chromatin —> open chromatin
DNA demethylation
His tone acetylation
Epigenetic marks
Features not directly dictated by genetic code which influences ways genes are expressed
DNA methylation
Histone modification
DNA methylation
Epigenic mark
Covalent motivation of dna
Transcription is suppressed in highly methylated regions of chromatin
Mediated by DMNT (DNA methyltransferase) where SAM (s-adenisymethione) is the methyl donor
Occurs in CpG islands - series of Cytosine and Guanine bonds
Histone modification
HDAC - histone deaceylation causes nucleosomes to pack tightly —> genes NOT EXPRESSED
HAT - histone acetylation causes loose packing of nucleosomes —> genes are EXPRESSED
RNAs in epigenetic regulation
ncRNA —> recruit specific chromatin including chromatin - modifiyinh protein complexes —> leads to gene silencing
Ex: X chromosome inactivation and genetic imprinting
Genomic imprinting
Parent dependent epigenetic marker
Copy from either mom or dad is expressed and one is silenced - silencing happens through DNA methylation
Zygote - establishment
Blosocyts, embryo - maintenance
Primordial germ cells - erasure by epigenetic demethylation
REVERSIBLE form of gene inactivation through generations - occurs during embryonic development
ARTS - cause epigenetic instability at erase, establishment and maintenance stages
Combo of infertility and/or multiple ARTs may cause greater risk for inducing epigenetic errors
Epimutation
Abnormal heritable change that causes an abnormal epigenetic regulation
Primary: occurs in germline and is present in all tissues —> DIRECT alteration of methylation pattern
Secondary: occurs in somatic tissue. DNA alteration at imprinting center (IC) INDIRECTLY alter methylation pattern
Epigenetic dysregulation
Trans generational inhereitance —> seen in FOURTH generation
Obesity
DNA methylation is GREATER in obese patients
In animals epigenetic switch!
Obesity and T2D
Variance of DNA methylation is GREATER in obese people
Epigenetic platters are cell specific and must look in:
Adipocyte tissue
Pancreatic islets
Skeletal muscle
Diet contains methionine and folate —> methyl donors
T2D decreased serum folate levels —> decreased methionine in liver
Increased dietary folate associated with lower risk of T2D
Physical activity in T2D
Exercise prevents or delays onset of T2D
Beneficial for glucose homeostasis —> less likely to develop insulin resistance
Acute or chronic exercise —> DNA methylation in skeletal muscle and adipose tissue
Epigenetic modifications are transient and reversible:
Prevention
Development of new therapies
Identification of epigenetic bio markers
Multiple sclerosis (MS)
Autoimmune disorder
Chronic demyelination disorder of CNS
2x as common in women could be due to epigenetic dysregulation —> X chromosome silencing “parent of origin effect”
Environmental risk factors: smoking influence epigenetic including DNA methylation, histone modification
Asthma
Chronic disease causing narrowed or swelled and mucus producing airways
Epigenetic markers: DNA methylation!!!!
Histone modification
ncRNA dysregulation
Exposure to air pollutants increase production of ROS which prevents interaction between DNMTs and DNA causing hypomethylated CpG sites
PAD
Peripheral artery disease
Clinical problems caused by narrowing, occlusion or aneurysm formation in peripheral arteries
MicroRNA. SMC apoptosis, phenotypic switch.————> PAD or AAA (abdominal
Histone mod. Inflammation. aortic aneurysm)
DNA methylation ——->. ECM degredation, migration
Angiogenesis
Epigenetic vs Static DNA
Epigenetic: semi conserved in meiosis and mitosis, functionally interacts with static DNA, RAPID evolutionary divergence, differs between cell types Amendable to pharmacological intervention
