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Flashcards in Lecture 11 Deck (38)
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1

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

T

2

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

Enhancer of zeste methylates lysine 27

3

What structures are referred to as the building blocks of chromatin

Nucleosomes

4

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

Lysine and arginine

5

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

Histone deacetylase and histone demethylase

6

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

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

7

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

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

8

How does methylation and acetylation of histone influence transcription

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

9

Explain the molecular mechanism of X-chromosome inactivation

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

10

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

11

Explain what is meant by X-chromosome inactivation

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

12

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

EZH2 methylates lysine 27

13

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

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

14

Specifically what is the effect of histone acetylation on gene transcription

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

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

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

16

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

Chromodomain

17

What ways can transcriptional repressors act to decrease gene transcription

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

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

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

19

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

F - Initial selection of the chromosome for silencing is random

20

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

Higher

21

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

PHD finger domains

22

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

Transcriptional activators containing PHD fingers

23

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

Transcriptional repressors containing chromodomains

24

What is the key difference between genetic and epigenetic modifications

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

25

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

T

26

Which residues are commonly acetylated by histone acetyltransferases

Lysine residues

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

28

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

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.

29

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

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

30

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

F – histone methyltransferase exhibit exquisite site specificities