Detailed revision notes on epigenetics from lecture course taught by Dr Biddie, University of Cambridge (now University of Edinburgh), with additional reading and insights from key publications summarised.
Regulation of Transcription
Dr Simon Biddie
simon.c.biddie@gmail.com
Lectures Outline and Objectives:
Lecture 1: Epigenetics and chromatin structure
Discuss the roles of regulation of histone modifications on transcription
Explain how chromatin remodelling complexes modify chromatin structure and
transcription
Understand the mechanism of DNA methylation and demethylation
Lecture 2: Dynamics of the epigenome
Understand the anatomy of the genome and discuss differences between enhancer and
promoter architecture
Explain the role of chromatin and transcription factors in cell identity
Discuss the dynamics of chromatin in differentiation and response to stimuli
Discuss how mutations in enhancers alter transcription factors binding and transcription
Lecture 3: Epigenetics and disease
Understand the role of chromatin structure in disease
Using epigenetic regulators as biomarkers and therapeutic targets
Essays:
Lecture 1:
Discuss how histone methylation regulates transcription
How do the mechanisms that regulate DNA methylation and histone modifications interact to
control transcription?
Lecture 2:
Chromatin is regulated by, and acts as a regulator of, transcription factor binding. Discuss.
Discuss the epigenetic and genetic factors that regulate enhancer activity.
Lecture 3:
How might changes in chromatin structure alter gene transcription in cancer?
Discuss how changes in DNA methylation might contribute to cancer and DNA methylation
regulators could be a therapeutic target
,Glossary:
, Lecture 1: Epigenetics and Chromatin Structure
Objectives:
Discuss the roles and regulation of histone modifications on transcription
Explain how chromatin remodelling complexes modify chromatin structure and
transcription
Understand the mechanisms of DNA methylation and demethylation
Gene Transcription and RNA Polymerase II
These lectures are not aimed at trying to understand how RNA is transcribed but rather
why RNA is transcribed.
Organisation of the Genome
The genome is organised into regulatory elements that include promoters and
enhancers that are important for transcription of genes.
DNA associates with histones into nucleosomes that fold and condense further into
higher order structures that make up chromatin. The more closely folded chromatin is,
the more inaccessible promoters and enhancers are to bindings factors and
transcription enzymes, the more resistant this region is to transcription. These regions
of closed chromatin are known as heterochromatin and open chromatin as
euchromatin.
Epigenetic mechanisms, that control gene expression, are inherited through
generations. Heritable non-DNA factors include histone modifications, histone variants,
chromatin remodellers, non-coding RNAs and DNA methylation.
Nucleosome Structure
A nucleosome is a unit of chromatin and consists of ~146 bp of DNA wrapped around
an octamer of histones that is made up of H2A, H2B, H3 and H4 in dimers. H2A and H2B
are more closely associated. These histones can be heavily modified, and these
modifications contribute to the compaction of the structure. Histone modifications
include Lys acetylation, Lys and Arg methylation, Ser, Thr and Tyr phosphorylation, Lys
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