Chapter 33 the control of gene expression in eukaryotes Flashcards
why are there different stable cell types
epigonome, differences in chromatin structure and covalent modification of DNA and not that the sequence is different
what do transcription factors do?
they interact directly with the transcriptional machinery and indirectly by changing chromatin structure
what is a chromatin
the entire complex of a DNA + the associated proteins
histone octamer
two units of H2A, H2B, H3 and H4
nucleosome core particle
145 bP + histones
which histone binds to linker DNA
H1
what does DNA form when wrapped around the histone core
a left-handed superhelix
what parts of the DNA do the histone core proteins interact with
inner face of DNA especially the phosphodiester backbone and the minor groove
why is the DNA wrapped around histone octamer as left-handed superhelix
because the left-handed direction stores negative supercoils, which can be used to underwind DNA when replication or transcription takes place
what part of transcription factor promotes transcription and how does it do it?
activation domain by interacting with RNA polymerase II, or by changing local chromatin structure or interacting with proteins that lead to the interaction with RNA polymerase II
classes of DNA-binding proteins in transcription factors in eukaryotes
Homeodomains
basic-leucin zipper proteins
cys2his2 zinc finger-domains
how can transcription factors for example act indirectly on RNA polymerase II?
through mediators interactions with the activation domains of transcription factors.
mediators faciltate the phorphorylation of the carboxyæ terminal of Polymerase
common features between activation domains
1- redundant: a part of it can be deleted without loss of function
2- modular: activate transcription when paired with a variety of DNA -binding domaains
3- act synergestically: acting together much stronger effect than acting alone
the opposite of mediators
transcriptional repressors
combinatorial control
proteins affecting the patterns of gene expression
enhancer
only effective when they are found in cells expressing the regulatory proteins that bind to them
they change the local chromatin structure rather than interacting directly with the RNA polymerase
Hypersensitive sites
regions adjacent to genes if transcribed are susceptible to cleavage by DNase 1 if not transccribed resistent to cleavage
DNA-methylation causes the ….. of transcription
inhibition
Which nukleotide can be methylated and describe the mechanism
cytosin
5-methyl group extends to the major groove and interferes with the binding of proteins that cause the stimulation of trascription
hypomethylation
absence of 5-methylcytosine near the start site
estrogen binds to and the mode of action
nuclear hormone receptors
Estrogen receptor
consensus sequence AGGTCANNNTGTCCT
binds as a dimer
DNA-binding domain lies at the center and consists of a set of zinc based domains bind to DNA via alpha helices inserted into the major groove.
Ligand binding site towards the carboxyl terminal
How does estrogen receptor and related receptors induce the change in gene expression
by attracting coactivators upon the binding of estrogen to the receptor SRC-1 (sterioid receptor coactivator 1)
GRIP-1 (glucocorticoid receptor interacting protein 1 )
NcoA-1 (nuclear hormone receptor coactivator 1)
the belong p160 family
Tamoxifin and Estrogen-receptor mediated pathway
blocks the binding of coactivators and inhibits the activation of gene expression
does that by binding to the bindings sites and thus block the normal conformational changes that lead to induce and cause the chromatin structureto change
. helix 12 can not pack into its usual position and therefore, the helix 12 will block the binding of the coactivator
histone acetyl-transferases which histone H3
transfer of acetyl from acetyl-CoA to lysin
some coactivators from p160 family can also do that
H3
what is a bromodomain
a domain in many eukaryotic regulatory proteins. Bind to peptides containing acetyllysine
proteins binding to TATA-box
TAFS (TATA-box-binding protein associated factors)
where are bromdomains present?
In TAFs and chromatin remodelling complexes/engines
chromatin remodelling complexes how do they work and what do they need?
ATP hydrolysis
they shift the positions of nucleosomes along the DNA and induce other conformational changes
how does acetylation work
1- reduced affinity
2- recruiting other components of the transcriptional machinery
3- shifting the positions of nucleosomes
they all activate transcription
what removes the acetyl group from histones
and what does this cause
histone deacetylases
the block of transcription by increasing the affinity of the histones for the DNA
why is excess of iron damaging
because there are not proteins enough to bind the iron and the iron will therefore be free to form many reactive radicals
to what end does the IRP bind to ferritin-mRNA
5’ end
to what end does the IRP bind to transferrin-mRNA
3’end
