BIOL 1500 Lecture Notes - Chromatin Remodeling, Tata Box, Regulatory Sequence

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Published on 20 Mar 2013
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Heena Loomba
Chapter 15: Control of Gene Expression
15.1 Regulation of Gene Expression in Prokaryotes
Prokaryotic cells undergo rapid and reversible alterations in biochemical pathways
that allow them to adapt quickly to changes in their environment
Sugars might be more available in the water environment, and genes to coding for
enzymes needed to metabolize this energy source need to be “turned on”
Other nutrients (ex. The amino acid tryptophan) may also be available in water. So
genes coding for the enzyme needed to make the amino acid “from scratch” need
to be “turned off”
Bacteria has a versatile and responsive control system allowing it to be efficient
when using nutrients
Gene expression in prokaryotes is regulated at the transcription level with genes
organized into functional units called operons
Operon function coordinates synthesis of proteins with related functions
15.2 Regulation of Transcription in Eukaryotes
Coordinated synthesis of proteins with related function occurs, but the genes are
scattered around genomes (not organized into operons)
Individual eukaryotic genes also consist of protein-coding sequences and adjacent
regulatory sequences
Short-term regulation: involves regulatory events in which gene sets are quickly
turned on or off in response to changes in environmental or physiological
conditions in the cell’s or organism’s environment
Long-term regulation: involves regulatory events required for an organism to
develop and differentiate, occurs in multicellular eukaryotes (not unicellular
Why is regulation of gene expression more complicated in eukaryotes?
Eukaryotic cells are more complex because nuclear DNA is organized with
histones into chromatin
Multicellular eukaryotes produce many different types of cells
Eukaryotic nuclear envelop separates the processes of transcription and
translation (do not happen simultaneously)
In eukaryotes there is transcriptional regulation, posttranscriptional regulation,
translational regulation and posttranslational regulation
Why does chromatic structure play an important role in gene activation?
Genes in DNA that are tightly wound around histones in chromatin are
inactive because their promoters are not accessible to the proteins that
initiate transcription
Heena Loomba
Chapter 15: Control of Gene Expression
Chromatin remodeling: changing the state of the chromatin so that the
proteins that initiate transcription can bind to their promoters in order to
activate a gene, opens the way for transcription to occur
Example of chromatin remodeling: an activator binds to a regulatory
sequence upstream of the gene’s promoter and recruits a remodeling
complex (protein complex that displaces a nucleosome from the chromatin)
exposing the promoter
Organization of a eukaryotic protein-coding gene
The promoter is found upstream of the transcription unit and contains the
TATA box
Transcription factors recognize and bind to the TATA box and recruit
polymerase (RNA polymerase II cannot bind on its own) RNA polymerase
II-transcription factor complex forms, the polymerase unwinds the DNA
and transcription begins
Promoter proximal region contains promoter proximal elements (regulatory
sequences) which increase the rate of transcription
Enhancer: contains regulatory sequences that determine whether the gene
is transcribed at its maximum possible rate
Activation of transcription
General transcription factors: proteins which initiate transcription, bind to
the promoter in the TATA box area, recruit the enzyme RNA polymerase II
and orients the enzyme to start transcription at the correct place
Transcriptional initiation complex: combination of general transcription
factors with RNA polymerase II, on its own it brings a low rate of
transcription initiation (leading to a few mRNA transcripts)
Activators: regulatory proteins that control the expression of one or more
genes, bind to the promoter proximal elements to increase rate of
transcription, interact with the general transcription factors to stimulate
transcription initiation
Housekeeping genes: genes expressed for basic cellular functions, have
promoter proximal elements that are recognized by activators present in all
cell types
Genes expressed in particular cell types or at particular times have
promoter proximal elements that are recognized by activators found only in
those cell types or at those times
Coactivator: large multiprotein complex, forms a bridge between the
activators at the enhancer and the proteins at the promoter and promoter
proximal region and causes the DNA to loop around on itself
Heena Loomba
Chapter 15: Control of Gene Expression
Interactions between the coactivator, proteins at the promoter and RNA
polymerase stimulate transcription to its maximal rate
Repression of transcription
Repressors oppose the effect of activators by blocking or reducing the rate
of transcription
Some repressors bind to the same regulatory sequence to which activators
bind (often in the enhancer) to prevent activators from binding to that site
Some repressors bind to their own specific site where the activator binds
and interact with the activator so it cannot interact with the coactivator
Some repressors recruit histone deacetylation enzymes that modify histones
causing chromatin compaction and making a gene’s promoter inaccessible
Combinatorial gene regulation
Characteristic of any given gene is the number and types of promoter
proximal elements
Number and types of regulatory sequences in the enhancer are specific to
each gene
Each different regulatory sequence in the promoter proximal region and
enhancers binds a specific regulatory protein
Combinatorial gene regulation: combining a few regulatory proteins in
particular ways so transcription of many genes can be controlled and many
cell types can be specified
A relatively small number of regulatory proteins control transcription of all
protein-coding genes
Different genes require different combinations of regulatory proteins, so the
number of genes encoding regulatory proteins is much lower than the
number of genes they control
Coordinated regulation of transcription of genes with related functions
Genes with related function are often clustered and they are transcribed
from one promoter onto a single mRNA. That mRNA is translated from one
end to the other to make the several proteins encoded by the genes
There are no operons in eukaryotes, but gene transcription is coordinated
All genes that are coordinately regulated have the same regulatory
sequences associated with them. One signal can control transcription of all
the genes simultaneously
Ex. Testosterone regulates the expression of genes associated with the
maintenance of primary and secondary male characteristics
Steroid hormone acts on specific target tissues in the body because only
cells in those tissues have steroid hormone receptors in their cytoplasm