Lecture 25: Epigenetics & Environmental Toxins Flashcards
nucleotide (3 parts)
5 carbon sugar + nitrogenous base + phosphate
nucleoside (2 parts)
5 carbon sugar + nitrogenous base
2 types of 5 carbon sugar
ribose, 2-deoxyribose
2 types of nitrogenous base
purine
pyramidine
nucleic acid
chain of nucleotides
codon
genetic code - sequence of three nucleotides that code for particular amino acid
2 purines
adenine
guanine
pyrimidines
cytosine
thymine
uracil
3 differences between DNA and RNA
- ribose sugar (deoxy ribonucleic acid vs ribonucleic acid)
- T & U (thymidine vs uracyl)
- strand (double vs single)
translation of mRNA to protein occurs on ___
ribosomes
three types of RNA
mRNA
tRNA
rRNA
the epigenome is an essential part of the nexus of ___
nature and nurture
3 most studied epigenetic mechanisms
- DNA methylation
- mods to histones
- microRNA regulation of DNA expression
DNA methylation
covalent attachment of methyl groups to particular regions of a gene, spec cytosine of a cytosine-guanine dinucleotide
effect of DNA methylation
reduce transcription of gene
chromatin
complex of small spherical histone proteins around which DNA wraps
what loosens chromatin structure?
acetylation, methylation, or phosphorylation of lysine residues of histone tails
nucleosome
segment of DNA wrapped around a histone octamer consisting of two copies each of four core histones
epigenetic modifications are critical for ___
cell differentiation
significant overeating leads to (2)
- genes for obesity overexpressed
2. genes for longevity underexpressed
DNA methylation enzyme
DNA methyltransferases (DNMT1 and DNMT3a)
histone acetylation enzyme
histone acetyltransferases (CREB-binding factor protein)
histone acetylation can be revesed by ___
histone deacetylases
DNA ticketing theory of memory
methyl groups added or removed from DNA could serve a persistent memory function
David Sweatt (3 conclusions)
pioneering epigenetic research
- DNMT activity necessary for experience-driven long-term behavioral change
- DNA methylation may work with histone mods to regulate memory formation and storage in adult CNS
- outcomes of epigenetic marks differ according to brain region and stage of memory formation
protein that increases in response to drug use
delta FosB
three categories of drug effects
- rapid response and tolerance
- accumulating and temporary abstinence
- enduring in abstinence
where is delta FosB rapidly induced? (2)
- nucleus accumbens
2. dorsal striatum
how does delta FoxB regulate gene transcription? (2)
- DNA methylation
2. histone mods
animals chronically exposed to drugs of abuse show elevated BDNF in ___
VTA
persistent organic pollutants (4 rqs)
synthetic organic compounds
- resistant to degradation
- low water solubility
- high lipid solubility
- high molecular weights
where do POPs accumulate?
aquatic food chain in fatty tissue
4 important POPs
- chlordane
- DDT
- polychlorinated byphenyls (PCBs)
- polychlorinated dibenzo-p-dioxins (PCDDs)
2 semi persistent organic pollutants
- bisphenol A (BPA)
2. polybrominated diphenyl ethers (PBDEs)
4 MoA of PCBs
- endocrine disruption
- alt in 2nd messenger systems
- interference in Ca2+ homeostasis
- inhibition of DA reuptake transporter
use of PBDEs
flame retardants in plastics and foam
congener of PBDEs still produced in Eu and US
decaBDE
where are PBDEs found? (5)
- air
- soil
- house dust
- food
- animals
use of PBDEs
flame retardants
3 effects of PBDEs
- perturbation of thyroid system
- alterations in signal transduction pathways
- alterations in sex hormones
BPA use
used in production of plastics
2 most frequent locations of PBA
epoxy-lined food cans and water bottles
primary MoA of PBA
endocrine disruption
chlordane type of pollutant
insecticide
chlordane half life
10-20 years
2 classes of insecticides
- organophosphates (OPs)
2. pyrethrins/pyrethroids
two uses of organophosphate
- insecticide
2. nerve gas
MoA of organophosphates
block AChE resulting in cholinergic syndrome
what pesticide promotes epigenetic transgenerational inheritance of adult-onset disease?
methoxychlor
methylbromide
insecticide, potent neurotoxin
MoA of pyrethrins/pyrethroids (2)
- disruption of voltage-gated Na+ channels (repetitive firing and increased Na+ influx)
- bind to and block GABA
MoA of lead
interference with calcium metabolism
Pb exposure is correlated with __ (3)
- IQ decline in children
- reduced grey matter in prefrontal cortex
- severe encephalopathy
MoA of mercury
inhibition of protein synth