PSIO 404 Exam 4 Flashcards
In complex with stimulatory
transcription factors,
histone
acetyltransferases (HATs) catalyze the
acetylation of histone Lysines to
“relax” the nucleosome and recruit
proteins with bromo domains
In complex with inhibitory
transcription factors
histone
deacetylase complexes (HDACs)
deacetylate histone Lysines to
“compact” the nucleosomal structure
and inhibit gene transcription.
V. Two Routes for Chromatin Activation
- The association of histones for DNA can be weakened by
mechanical force (Swi/Snf ATPases) - The association are also be weakened by covalent
modifications to histone proteins.
1. Acetylation = Lys
2. Methylation = Arg, Lys
3. Phosphorylation= Ser and Thr
4. Ubiquitinylation= Lys
5. Poly(ADP-ribosylation) = Lys
*lys also uses sumoylation
inactive versus active chromosome
Condensed chromatin
(DNA + histones) is
called “inactive”
Unfolded chromatin is
called “active”
Gene-Specific Transcription Factors
binds to specific DNA
sequences called response elements.
Design of a Typical Gene-Specific
Transcription Factor
- DBD = DNA-binding domain
- RD = regulatory domain
- TAD = transactivating domain
Activators
are signal-activated, gene-specific transcription factors which recognize (bind to) specific response elements.
The phosphorylation of many Ser & Thr residues is required to
remove H1 from the linker DNA region between nucleosomes and generate active (unfolded) chromatin.
H1
H1 kinase and enzymes catalyzing core histones modification
H1 phosphates and enzyme eliminate core histone modifications
Unfolding of chromatin
starts w/ phosphorylation
of H1 Ser/Thr residues by
H1 kinases
the five types of histones
H1 = linker
H2A, H2B, H3, H4 = core histones (these wrap 1.8 turns of DNA into a nucleosome)
Briefly explain how the cell integrates information.
Signals bind receptors which induce intracellular signaling. All meaningful (non-filtered
out) intracellular signaling has an effect on the genome, be it minor (altering proteins such
as histones slightly) or major (inducing major changes in gene expression). In the latter
case, the result is an altering of the makeup of the data-processing protein network (brain)
of the cell
How does nearly every cellular signal physically change the cell?
The moment-to-moment summation of signaling effects on the genome influences
immediate or future behavior of the cell, and in this way a cell has 1. memory and 2. learns
from its environment as well as it is able. This is cellular comprehension of the world
around it, and this comprehension is the basis for a cell’s exhibition of “responsiveness”
a cell does this to alter it DPPN to become less error prone
Define transcription factors, and explain how they work.
a transcription factor are proteins that control gene transcription by interacting with DNA motif (promoters enhancers, and silencers) to favor or prevent the binding and progression of RNA polymerase which will form RNA and DNA templates
Compare and contrast hydrophilic vs. lipophilic signaling with regard to transcription.
hydrophilic (loves water) = involves binding to membrane receptors and employing second messengers that lead to covalent modifications of TF
lipophilic(loves fat)= involves binding to nuclear receptors that lead to non covalent modifications of TF
combinatorial strategy
Genes are regulated by combinatorial strategy. A gene is generally controlled by several response
elements, each of which interacts with an individual transcription factor.
Termination
- At the end of the gene, changes in phosphorylation in RNAPII’s CTD
recruits 3’-end processing factors and leads to dissociation. - A dissociated RNAPII is reset for reinitiation of transcription by CTD
phosphatases.
Initiation
Activator binding triggers assembly of pre-initiation complex.
* Phosphorylation of RNA polymerase II’s repeating heptapeptide C-terminal
domain (CTD) at Ser5 by TFIIH forms a scaffold.
TFIIH = CAK = CDK7/cyclinH
Elongation
- Thanks to Ser5 phosphorylation in RNA polymerase II’s (RNAPII’s) CTD, the
mRNA is 5’ capped. - CDK9/cyclinT(K) phosphorylation at Ser2 in RNAPII’s CTD recruits
elongation factors and mRNA processing enzymes.
Name and briefly describe the three phases of gene transcription.
initiation = begins with the formation of an initiation complex at a gene region as the promoter this region is marked in advance by TF that recognize the nucleotide sequence of the promoter DNA motif
Elongation = initiation complex is replaced by an elongation complex
termination = transcription ends with dissociation of an elongation complex upon reaching the terminator gene region
Describe the components of the transcription initiation complex.
-the initiation complex is formed by RNA polymerase II and the TFII family general TF
-TFIID binds to DNA at the promoter and nearby regions
Describe how general and specific transcription factors are alike and how they are different with regard to their functions.
general TF – In combination with RNA polymerase II, these constitute the “basic machinery” required for transcription.
– Assemble at promoters bound by a Gene-Specific TF
Specific TF binds to specific DNA
sequences called response elements.
-Response elements are in promoters, enhancers, and silencers.
Describe response elements. How is the expression of 25,000 human genes controlled by only 707 human response elements?
A gene is generally controlled by several response elements, each of which interacts with an individual transcription factor. In this way, genes are regulated by a combinatorial strategy
-Via a combinatorial strategy, the 6% of our genome (genes) which encodes
transcription factors can control all gene activity.
* Additional proteins, called co-activators and co-repressors are involved as well (enhanceosomes)
Histones & Nucleosomes
- Five major types
– 1 linker histone: H1
– 4 core histones: H2A, H2B, H3, and H4. - The 4 core histones wrap 1.8 turns of DNA into a nucleosome
Describe two routes for how chromatin is activated.
To activate H1 kinases and enzymes catalyzing core histone modifications that allow availability of the linker region of DNA to allow gene specific TF can interact with them
1. The association of histones for DNA can be weakened by mechanical force (Swi/Snf ATPases) by constantly pushing on DNA to move them off histones make them available quicker
2. The association are also be weakened by covalent modifications to histone proteins
To inactive H1 phosphatase and enzymes eliminating core histones modifications and encourage a region of DNA to become inactive (condensed)