Lecture 11 Flashcards
In general transcription activators promote RNA polymerase II recruitment, T or F
T
Which residue does enhancer of zeste act on and what type of modification is it
Enhancer of zeste methylates lysine 27
What structures are referred to as the building blocks of chromatin
Nucleosomes
Histone methyltransferases mono, di or trimethylated which amino acids within the histone tails
Lysine and arginine
What are the names of the enzymes that reverse histone acetylation and methylation respectively
Histone deacetylase and histone demethylase
Acetylation and methylation of core histone tails can occur simultaneously, T or F
F – methylation and acetylation are mutually exclusive and are competing modifications
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
How does methylation and acetylation of histone influence transcription
Acetylation and methylation marks in general create binding sites for transcription factors
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
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
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
Enhancer of zeste is one enzyme that methylates a lysine residue. What position in the polypeptide chain does it act
EZH2 methylates lysine 27
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
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.
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
Methylation of core histones creates binding sites for transcriptional repressors that contain what kind of domain
Chromodomain
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
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
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
Will genes that are more transcriptionally active show higher or lower levels of acetylation
Higher
Methylation of core histones creates binding sites for transcriptional activators that contain what kind of domain
PHD finger domains
Which type of transcription factors will bind to methylated lysine 4 and arginine 17 residues
Transcriptional activators containing PHD fingers
Which type of transcription factors will bind to methylated lysine 9 and 27 residues
Transcriptional repressors containing chromodomains
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
Histone acetyltransferases can modify many different lysine residues, T or F
T
Which residues are commonly acetylated by histone acetyltransferases
Lysine residues
What is the role of EZH2 in development
EZH2 is a gene required to repress Hox gene expression in a specific anterior-posterior fashion
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.
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
Histone methyltransferases can modify many different lysine or arginine residues, T or F
F – histone methyltransferase exhibit exquisite site specificities
Explain how H3K27 and H3K9 leads to the formation of a Barr body
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
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
How did Conrad Waddington describe how cells differentiate due to epigenetic changes
Cells traverse and epigenetic landscape of various differentiation possibility which gradually restricts cell fates
Reversibility of the acetylation and methylation of histones accounts for what attribute of epigenetic changes
Means that they can be removed – aren’t permanent
How are the progeny of the cell that silences one of the X chromosomes in somatic female cells affected
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
Why are regions on the face, neck, bely and white still white in calico cats, despite X-chromosome inactivation
These regions don’t contain pigment cells
Lysine acetylation is an indication of what
Transcriptionally active genes
Histone methyltransferases act as regulators of gene transcription and are uniquely site specific, T or F
T
