Epigenetics Flashcards
topics under current investigation:
- short term memory (sec-hrs)
- long term memory (decades)
- trauma
- children’s aggression
- drug addiction
- depression
- suicide
who attends conferences on epigenetics & behavior?
- anthropologists
- geneticists
- neuroscientists
- molecular bioligists
- psychiatrists
- psychologists
what is epigenetics? (old definition)
-heritable changes in a phenotype in the absence of alterations of the DNA sequence
new definition of epigenetics:
-any lasting change in gene expression mediated by alteration in chromatin structure
chromatin=
-DNA plus proteins
what is gene expression?
- transcription of DNA code in RNA by RNA polymerase (mRNA, tRNA, rRNA, microRNA)
- translation of mRNA into proteins
what controls gene expression?
- proteins can change the shape of the DNA, making some regions of DNA available for transcription and some unavailable
- histones, non-histone proteins & transcription factors
what are histones?
- proteins that DNA is wrapped around.
- they can make DNA available or unavailable for transcription
what are transcription factors?
-proteins that can bind to DNA at promoter and enhancer sites (noncoding DNA regions) and alter the shape of DNA
alteration of gene expression causes=
-cell differentiation
what regulates transcription factors activity?
- many primary messenger molecules such as: NP, hormones & cytokines, regulate gene transcription
- some, such as steroid hormones bind directly to transcription regulating proteins (aka->hormone receptors) that bind to regions of DNA called hormone response elements
regulation of transcription factors thru phosphorylation:
- other primary messengers regulate phosphorylation of transcription factors by activating protein kinases that phosphorylate the transcription factors
- i.e. regulation of gene expression by cyclic AMP
regulation of phosphorylation by receptors with tyrosine kinase activity:
-many growth factors as well as insulin influence cells this way
the roles of non-coding DNA:
- noncoding DNA=DNA that is not transcribed to RNA=90% of human genome
- sites for the binding of transcription factors
- after binding transcription factors, the DNA can fold or unfold in various ways that influence the availability of a coding region of DNA for transcription to RNA
mutations of noncoding DNA regions can lead to disease without a mutation of a known gene:
- noncoding DNA mutations have been found that increase a person’s risk for developing:
- coronary artery disease
- cancer: prostate, colorectal
- extra fingers & toes
- excessive inflammation
changes in gene expression: inactivation
- methylation (CH3) of histone tails and/or sequences of DNA can change the physical relationship b/w the DNA & histone
- methylation can “silence” a gene making the gene unavailable for transcription to RNA
- methylation of DNA permanently silences a gene but methylation of histone is reversible
changes in gene expression:
activating marks
- methylation
- acetylation
- phosphorylation
- histone remodeling complexes
Enzymes that control epigenetic marks:
- histone methyl transferase
- histone demethylase
- histone acetyl transferase
- histone deacetylase
- these enzymes are coded for by genes whose expression can be controlled by epigenetics
epigenetics & cancer:
- cancer cells can experience methylation of tumor suppressor genes making them unavailable for expression
- microRNA’s can bind to complimentary regions of mRNA’s & prevent the mRNA from being translated into protein
- hyper methylation of DNA that codes for micro RNA’s which bind to mRNA’s that code for factors that regulate growth
epigenetics & the brain:
effects on memory=
- methylation & demethylation occurs continually in the adult brain.
- it effects formation & retention of memory
changes in the brain due to childhood abuse:
- more DNA methylation in genes for ribosomal RNA in the hippocampus
- of 18 men who committed suicide after experiencing abuse as children
- compared to 12 brains of men who died suddenly who had no record of childhood abuse
- of brains of men who committed suicide who had not experienced childhood abuse
methylation of immune T cell DNA associated with behavior:
-boys with high aggressive behavior had decreases cytokine blood levels & more mehtylation of genes coding for cytokines
epigenetic events in addiction & depression:
- observations in identical twins susceptibility or resistance to addiction and depression
- 50% genetics; 50% life experience
epigenetics changes can be caused by:
- random environmental events during embryonic & fetal development
- drug use-> epigenetic changes that activate cravings for addictive substances
- chronic stress->feelings of defeat->decreased activation of reward center->depression
