16: Epigenetics

epigenetics

study of effects of reversible chemical modifications to DNA and/or histones on the pattern of gene expression

• do not alter the nucleotide sequence of DNA (heritable independently from DNA sequences)

• observed in bacteria, plants, humans and animals

epigenome

specific pattern of epigenetic modifications present in a cell or a given period in time

• multiple epigenome during an organism’s lifespan

epigenetics can affect

• behaviour

• reproduction

• disease processes

• adaptation to the environment

causes of epigenetics

• diet

• toxins

• chemicals

• stress

DNA methylation

reversible modification of DNA expression by the addition/removal of methyl groups

DNA methylation steps

after DNA replication and during cell differentiation

• DNA methyltransferase (DMNT) adds a methyl group to cytosine adjacent to a guanine (CpG islands)

• blocking the binding of transcription factors or RNA polymerase

= decrease in the rate of transcription

housekeeping gene

constitutive gene i.e., transcribed constantly

• maintains basic cellular function

• genes involved in cell cycle transcription RNA processing, etc.

• they are hypomethylated

histone modifications

chromatin remodelling by the addition/removal of chemical groups to histone proteins

• i.e., covalent post-translational modifications of amino acids near the N-terminal ends of histone proteins

• gene transcription is either activated or repressed through changes in the condensation of the chromatin

acetylation

histone modification that increases the availability of DNA for transcription

• remodels chromatin structure to euchromatin

histone acetyl transferase (HAT)

adds acetyl to lysine

histone deacetylase (HDAC)

removes acetyl from lysine

methylation

inhibit or increase the availability of DNA for transcription

• transforms chromosome structure to either euchromatin or heterochromatin depending on the effect

writers

are enzymes that modify histones by adding acetyl or methyl groups

erasers

are enzymes that modify histones by removing acetyl or methyl groups

readers

are enzymes that further modify chromatin structure and regulate transcription by

1. recognizing epigenetic marks

2. recruiting other proteins (TFs, chromatin remodelers)

3. modulating chromatin structure (e to h)

histone code

hypothesis stating that transcription of genetic information is partly regulated by histone modifications and their interactions

• some modifications can interact with other modifications and combine

non-coding RNAs

RNA molecules that don't code for proteins and regulate gene expression

epigenetic inheritance

inheritance of traits transmitted by mechanisms not directly involving the nucleotide sequence of a genome

impact of epigenetic inheritance

modifications carry through a few rounds of replication and can therefore be transmitted from one generation to the next

however:

• often reset during the formation of gametes

• unstable and dissipate

• short-term impact, not long-term evolutionary change

Lamarack’s Theory

believed that adaptive variation arose because it was needed

• “organisms evolved through the use and disuse of organs with changes acquired during an organism’s lifetime being passed down to offspring”

conceptual link with epigenetics and lamarck

both suggest that acquired traits can be passed on to offspring

one-to-one connection

epigenetic modifications are not always a direct one-to-one connection/direct mirroring between an environmental factor and specific modification inherited trait

• traits that emerge in subsequent generations depend on how those changes influence gene networks, developmental pathways, etc.

examples of epigenetic inheritance

1. children of individuals exposed to famine showed altered metabolism and health risks

2. diet-induced DNA methylation changes in pregnant agouti mice affected coat colour and obesity risk in offspring

3. in rats, environmental stress in one generation = epigenetic modifications affecting behaviour in subsequent generations

4. epigenetic changes to NS during AD, Parkinsons, HT, schizophrenia, and BPD