Lecture 14 - Epigenetics Flashcards
What processes regulate transcription and how do they do it?
- Acetylation and methylation of histones by influencing recruitment of transcription factors to target genes
What characteristic feature of tumours is related to epigenetic ?
Over expression or mutation of histone-modifying proteins
What are the future prospects of epigenetics ?
Drugs that target the epigenetic machinery are promising new anticancer agents
Epigenetic traits
are stable, heritable phenotypes resulting from changes to chromatin structure without alterations to DNA sequences
What is the difference between genetics and epigenetics ??
Genetics – Mutation of DNA > altered gene function > Altered phenotype
Epigenetic’s – alterations to chromatin structure > altered gene expression > altered phenotype
Through regulating chromatin structure, what do epigenetic mechanisms do ?
- control accessibility of target genes to incoming transcription machinery
- Directly control biochemical activity of transcription machinery
Epigenetic modifications
cause stable alterations to chromatin structure
and gene expression but do not change nucleotide sequence of DNA
Give examples of epigenetic modifications:
- Histone modifications – acetylation, methylation
- DNA methylation
- non-coding RNAs
Production of differentiated cells from proliferating progenitor cells involves selective transcription of specific genes which:
- suppress self-renewal
- promote lineage commitment
- activate one programme of cell differentiation and repress all others
Conrad Waddington
epigenetic landscape / journey all cells take through development
- intracellular signalling pathways
early development- cells lie in higher reaches not exposed to env then move through the landscape and succumb to various signals and adopt specific cell fates
sequential changes in transcriptome and proteome
Cancers can develop when ?
self-renewing stem/progenitor cells “get stuck” in the higher reaches of the epigenetic landscape
What causes epigenetic induced cancers ??
Chromatin in nucleus acquires tumour specific characteristics
Modification targeted to the N terminal tail of the histone
- covalent modifications
Covalent modification added to core histones
- Acetylation of lysines in core histone N-terminal tails
- Mono-, di-, tri-methylation of lysines and arginines in core histone N-terminal tails. Various residues modified by distinct enzymes
- Phosphorylation of serine 10 in Histone H3
General epigenetic change that causes cancer -
Modify way transcription machinery interact
What happens to lysines if acetylated??
they can no longer be methylated
Whats the difference between HATs and HMTs ??
Histone Acetyltransferases (HATs) can modify many different lysine residues
in core histones whereas histone methyltransferases (HMTs) exhibit exquisite
site-specificities - “Histone Code” Writers
EZH2
- Specific mark on histone 2 lysine 7 – implicated in cancer
If chromatin rich in lysine 27
transcriptionally inactive