Lecture 11

Question 1

In general transcription activators promote RNA polymerase II recruitment, T or F

Answer 1

T

Question 2

Which residue does enhancer of zeste act on and what type of modification is it

Answer 2

Enhancer of zeste methylates lysine 27

Question 3

What structures are referred to as the building blocks of chromatin

Answer 3

Nucleosomes

Question 4

Histone methyltransferases mono, di or trimethylated which amino acids within the histone tails

Answer 4

Lysine and arginine

Question 5

What are the names of the enzymes that reverse histone acetylation and methylation respectively

Answer 5

Histone deacetylase and histone demethylase

Question 6

Acetylation and methylation of core histone tails can occur simultaneously, T or F

Answer 6

F – methylation and acetylation are mutually exclusive and are competing modifications

Question 7

Transcriptional activators recruit ATP-dependant chromatin remodelling enzymes, what four ways can these enzymes act to upregulate gene transcription

Answer 7

Selective histone octamer and whole nucleosome remodelling, selective histone removal and replacement and/or by recruiting code writers and readers

Question 8

How does methylation and acetylation of histone influence transcription

Answer 8

Acetylation and methylation marks in general create binding sites for transcription factors

Question 9

Explain the molecular mechanism of X-chromosome inactivation

Answer 9

X-chromosome inactivation involves the synthesis of a non-coding RNA known as Xist from the X-inactivation centre (XIC) on the chromosome destined for inactivation. Xist RNA binds to the X chromosome and acts as a recruitment signal to promote the formation of silent chromatin. This is achieved by recruitment of histone modifying enzymes and other Polycomb Group components and leads to the Histone-3 lysine 27 and H3K9 methylation of core Histones in X chromosome chromatin

Question 10

What is meant by histone code writers

Answer 10

Histone methyltransferases are histone code writers, they act as an additional code on top of the genetic code i.e. epigenetic to

Question 11

Explain what is meant by X-chromosome inactivation

Answer 11

X-chromosome inactivation is a process that occurs in mammals and acts as a dose compensation mechanism that equalizes the levels of X-chromosome derived gene products in males and females. One X chromosome copy is silenced in each somatic cell during early development of female embryo

Question 12

Enhancer of zeste is one enzyme that methylates a lysine residue. What position in the polypeptide chain does it act

Answer 12

EZH2 methylates lysine 27

Question 13

As well as histones, DNA can also be modified by methylation. When and how does this occur

Answer 13

There is a close functional relationship exists between transcriptionally repressive histone methylation and corresponding DNA methylation on cytosine bases. The addition of methyl groups to cytosine residues is mediated by DNA methyltransferases (DNMTs). Transcriptionally inactive promoters are frequently rich in methylated CpG dinucleotides

Question 14

Specifically what is the effect of histone acetylation on gene transcription

Answer 14

Acetylation of histones creates binding sites for transcriptional activation factors that contain a bromodomain. Histone Acetylation is associated primarily with transcriptionally active promoter sequences.

Question 15

Methylation can denote transcriptionally active or inactive genes depending on the loci of the residue. Determine whether methylation of lysine 4, 9, 27 and arginine 17 denote transcriptional activation or repression

Answer 15

Arginine 17 and Lysine 4 – transcriptionally active. Lysine 9 and 27 – transcriptionally inactive

Question 16

Methylation of core histones creates binding sites for transcriptional repressors that contain what kind of domain

Answer 16

Chromodomain

Question 17

What ways can transcriptional repressors act to decrease gene transcription

Answer 17

Compete for activator binding sites, prevent bound activators from functioning, keep transcriptional activators and transcription machinery away from the start site and also reverse effects of transcriptional activators by creating dense transcriptionally inert chromatin. Finally, they can also recruit enzymes such as histone demethylases and deacetylases as well as methyltransferases

Question 18

Epigenetic modifications facilitate stable changes in gene expression which may persist or the life of the cell of organism but are erased in the germ line, T or F

Answer 18

F – whilst the statement is true, epigenetic modifications are transferred to the progeny these cells can then decide whether to remove the epigenetic change

Question 19

The X-chromosome copy that is silenced is determined by maternal gene expression in the fertilised oocyte, T or F

Answer 19

F - Initial selection of the chromosome for silencing is random

Question 20

Will genes that are more transcriptionally active show higher or lower levels of acetylation

Answer 20

Higher

Question 21

Methylation of core histones creates binding sites for transcriptional activators that contain what kind of domain

Answer 21

PHD finger domains

Question 22

Which type of transcription factors will bind to methylated lysine 4 and arginine 17 residues

Answer 22

Transcriptional activators containing PHD fingers

Question 23

Which type of transcription factors will bind to methylated lysine 9 and 27 residues

Answer 23

Transcriptional repressors containing chromodomains

Question 24

What is the key difference between genetic and epigenetic modifications

Answer 24

Genetic alterations occur to the DNA sequence directly and permanently affect gene expression. Epigenetic alterations occur to chromatin structure and act to modulate gene expression. These do not alter the DNA sequence and are reversible

Question 25

Histone acetyltransferases can modify many different lysine residues, T or F

Answer 25

T

Question 26

Which residues are commonly acetylated by histone acetyltransferases

Answer 26

Lysine residues

Question 27

What is the role of EZH2 in development

Answer 27

EZH2 is a gene required to repress Hox gene expression in a specific anterior-posterior fashion

Question 28

Explain how X-chromosome inactivation accounts for tortoiseshell or calico cats

Answer 28

Calico cats are exclusively female. They are heterozygous for two coat pigment alleles, black and orange. Early in development in progenitor cells either orange or black alleles are inactivated. Where black pigment allele containing X-chromosomes are switched off, all progenitors will produce fur orange in colour. Where orange pigment allele containing X-chromosomes are switched off, all progenitors will produce fur black in colour.

Question 29

Explain the role of enhancer of zeste in hox gene repression and the involvement of polycomb repressive complexes

Answer 29

Enhancer of zeste is the catalytic subunit that acts as part of a complex that represses hox gene expression. PRCs contains chromodomains and methylate lysine 27 loci toproduce global derepression of hox genes

Question 30

Histone methyltransferases can modify many different lysine or arginine residues, T or F

Answer 30

F – histone methyltransferase exhibit exquisite site specificities

Question 31

Explain how H3K27 and H3K9 leads to the formation of a Barr body

Answer 31

Lysine 9 and 27 methylation along the entire length of the X chromosome leads to the entire silencing of the chromosome and its shunting to the periphery of the nucleus. This leads to the production of a Barr Body, a highly condensed inactive X chromosome at the periphery of the nucleus of every female somatic cell

Question 32

What is significant about the tails of core histones

Answer 32

Nucleosome core histones have N-terminal lysine rich tails which project radially from the core. These can be reversibly covalently modified

Question 33

How did Conrad Waddington describe how cells differentiate due to epigenetic changes

Answer 33

Cells traverse and epigenetic landscape of various differentiation possibility which gradually restricts cell fates

Question 34

Reversibility of the acetylation and methylation of histones accounts for what attribute of epigenetic changes

Answer 34

Means that they can be removed – aren’t permanent

Question 35

How are the progeny of the cell that silences one of the X chromosomes in somatic female cells affected

Answer 35

The silencing decision is propagated clonally and all progeny of each cell in which the silencing decision was taken inherit the same silenced X chromosome

Question 36

Why are regions on the face, neck, bely and white still white in calico cats, despite X-chromosome inactivation

Answer 36

These regions don’t contain pigment cells

Question 37

Lysine acetylation is an indication of what

Answer 37

Transcriptionally active genes

Question 38

Histone methyltransferases act as regulators of gene transcription and are uniquely site specific, T or F

Answer 38

T