NEUS 609 - CNS Epigenetics & Gene Expression

transient

___ neural adaptations are due to cytoplasmic secondary messengers and protein phosphorylation.

• change in enzymes such as kinases and cAMP

• deal with proteins NOT genes

• active almost immediately

stable

___ neural adaptations are due to transcription factors (such as CREB) altering gene expression in the nucleus.

• deal with genes NOT proteins

• take time to be put in place

central dogma

DNA > mRNA > Proteins

unidirectional

the central dogma is mostly ___, meaning that mutations in DNA affect everything, while mutations in protein s only affect protein functions.

• only naturally occurring exception is HIV

transcription

process of making RNA from DNA

translation

process of making proteins from RNA

Genetics

basically DNA

sequence of nucleotide bases that make up an individual’s genes and non-coding regions

• the sequence itself

Epigenetics

something that alter the gene expression WITHOUT altering the DNA sequence itself

• epi = above in ancient greek so ___ means above genetics

• anything controlling how DNA sequence is accessed and read without modifying it

gene elements

• 5’ cap

• 5’ untranslated sequence (still transcribed, usually correpsonf to promoter region)

• start codon

• coding region

• stop codon

• 3’ untranslated region (still transcribed)

• poly A tail (contain stop sequence for transcription)

initiation

first step of transcription

RNA polymerase II binds to sigma factor and associate with promoter region. DNA strands open by helicase.

elongation

RNA polymerase II read DNA and create corresponding mRNA strand at the same time

termination

RNA polymerase II reach the stop sequence in the poly A tail and release the now complete mRNA molecule

large

RNA polymerase II is very __ molecule

Transcription factors

aka TFs

proteins that bonds either directly to the DNA strand or to a complex of other proteins that aid in transcription

• target specific DNA sequence, often promoter regions and TATA box

• recruit polymerase II and other TFs

• can be activating or repressing

• different TFs in different cell types

• can be turned on/off by other TFs

chromatin

3D structure of DNA made of the DNA and histone proteins

• help all 2m of DNA fit into cell nucleus

• help determine TF/transcriptional machinery access to the genes

euchromatin

loose form of chromatin

• permissive

• genes accessible

heterochromatin

tightly packed form of chromatin

• repressive

• genes are NOT accessible

factors that modify gene expression

• histone tail modificaitons

• DNA methylation

• microRNAs

Acetylation

when an acetyl group is added to a lysine residue in histone tails

• acetyl group and DNA are both negatively charged and thus repel each other

• the acetyl group makes the tail bulkier and thus take more space

• promote euchromatin

• DYNAMIC

Methylation

when a methyl group is added to lysine residue in histone tails

• promotes heterochromatin

• interfere with TFs binding

• DYNAMIC

• histone methyltransferases (HMTs) put methyl group on

• histone lysine demethylases (KDMs) take methyl group off

DNA methylation

adding of methyl group on cysteines followed by guanines aka CpG sites in DNA sequence

• interfere with TFs binding

• dependent on folate aka methyl donor in your diet

• STABLE because inheritable across cell division

• DNA methyltransferases (DNMTs)

DNMT 3A

de novo DNA methylation aka methylate embryonic DNA

DNMT 1

maintenance DNA methylation

CpG sites

cysteines followed by guanines in DNA sequence

usually cluster in promoter regions in islands

regions that get methylated

• usually hypomethylated in normal somatic cells, so hypermethylation prevent TFs access

microRNAs

non-coding RNA about 22 nucleotides long produced from their own genes or from introns of targets/other genes

• hairpin loop of RNA formed, expelled of nucleus, cut by DICER enzyme, and then bind to RISC complex to stop specific translation

• DYNAMIC

nature, nurture

epigenome is the link between the genes (__) and the environment (__)

• identical twins study where they have different epigenomes years and decades later while they had the same pattern when they were young

maternal care

rats licking behavior aka ___ is influent on epigenetics

• more licking = less stress response = less methylation of glucocorticoid receptor genes

• less licking = more stress = more methylation