Lecture 10 Epigenetics and Cancer Flashcards
What are the two ways that regulating chromatin structure can be used to regulate gene expression
Controlling the accessibility to target genes of the transcription machinery and controlling the biochemical activity of the transcriptional machinery itself
How do epigenetic modifications differ from genetic modifications
Epigenetic modifications cause stable alterations to the chromatin structure but unlike genetic alterations these are reversible and do not involve changing the nucleotide sequence of DNA
What are the three broad categories of epigenetic modifications
Histone modifications (acetylation and methylation) DNA methylation and non-coding RNAs
What was Conrad Waddington’s contribution to the field of epigenetics
Conrad Waddington suggested that different cell fates during development are the end results of distinct journeys through an epigenetic landscape
In order for a haematopoietic stem cell to produce differentiated leukocytes and erythrocytes what phenomena need to occur
It needs to repress its ability to self-renew activate of program of lineage commitment and execute a program of terminal differentiation
What structures are referred to as the building blocks of chromatin
Nucleosomes
What is the effect of covalent modification of nucleosomes
Nucleosomes can be covalently modified which act as structural changes to the chromatin that effect gene transcription
What is significant about the tails of core histones
Nucleosome core histones have N-terminal lysine rich tails which project radially from the core. These can be reversibly covalently modified
Which residues are commonly acetylated by histone acetyltransferases
Lysine residues
Histone methyltransferases mono di or trimethylate which amino acids within the histone tails
Lysine and arginine
Acetylation and methylation of core histone tails can occur simultaneously T or F
F – methylation and acetylation are mutually exclusive and are competing modifications
Production of methylation marks prevents acetylation T or F
T
Histone acetyltransferases can modify many different lysine residues T or F
T
Histone methyltransferases can modify many different lysine or arginine residues T or F
F – histone methyltransferase exhibit exquisite site specificities
How many different enzymes methylate lysine 4 residues
6 different enzymes
How many different enzymes methylate lysine 9 residues
5 different enzymes
Which residues are methylated by CARM1
Arginine 17
Enhancer of zeste is one enzyme that methylates a lysine residue. What position in the polypeptide chain does it act
EZH2 methylates lysine 27
What is the role of EZH2 in development
EZH2 is a gene required to repress Hox gene expression in a specific anterior-posterior fashion
Histone methyltransferases act as regulators of gene transcription and are uniquely site specific T or F
T
Histone acetylases are uniquely site specific T or F
F – they acetylate a number of different lysine residues
What is meant by histone code writers
Histone methyltransferases are histone code writers they act as an additional code on top of the genetic code i.e. epigenetic to
What are the names of the enzymes that reverse histone acetylation and methylation respectively
Histone deacetylase and histone demethylase
Reversibility of the acetylation and methylation of histones accounts for what attribute of epigenetic changes
Means that they can be removed – aren’t permanent
Lysine acetylation is an indication of what
Transcriptionally active genes