Download Biol115_2014_Lecture 12_Eukaryotic Gene Regulation

Biol115
The Thread of Life"
Lecture 11"
Regulation of gene expression II: "
Eukaryotic Transcription and cellular
differentiation"
The body is a community made up of its innumerable cells or
inhabitants"
~Thomas A. Edison"
Principles of Biology"
•  Chapter ‘Eukaryotic gene regulation’."
Biol115_2014_Lecture 11"
2"
Objectives"
•  Describe the variety of mechanisms for gene
regulation in eukaryotic cells."
•  Describe the role of chromatin (chromosome
folding) in gene regulation."
•  Explain how transcription factors offer
multiple opportunities for gene regulation."
•  Explain how gene expression is co-ordinately
controlled in eukaryotes."
•  Explain how differential gene expression
leads to programs of cellular specialisation."
"
Biol115_2014_Lecture 11"
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Eukaryotic gene expression
is regulated at many stages"
•  All organisms must regulate which genes
are expressed at any given time"
•  In multicellular organisms regulation of
gene expression is essential for cell
specialisation."
Biol115_2014_Lecture 11"
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Chromosome packaging and
gene expression"
Non-coding RNA
(e.g. siRNA) can
convert euchromatin
into non-expressed
heterochromatin."
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Differential Gene Expression"
•  Almost all the cells in an organism are
genetically identical"
•  Differences between cell types result
from differential gene expression, the
expression of different genes by cells
with the same genome"
•  Gene expression is regulated at many
stages"
Biol115_2014_Lecture 11"
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Regulation of
Transcription Initiation"
•  Associated with most eukaryotic genes are
multiple control elements, segments of
noncoding DNA that serve as binding sites
for transcription factors that help regulate
transcription"
•  Control elements and the transcription
factors they bind are critical to the precise
regulation of gene expression in different
cell types"
Biol115_2014_Lecture 11"
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Enhancers and Specific
Transcription Factors"
•  Proximal control elements are
located close to the promoter"
•  Distal control elements, groupings of
which are called enhancers, may be
far away from a gene or even located
in an intron"
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The Roles of Transcription
Factors"
To initiate transcription, eukaryotic RNA
polymerase requires the assistance of
proteins called transcription factors!
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•  An activator is a transcription factor that
binds to an enhancer and stimulates
transcription of a gene"
•  Some transcription factors function as
repressors, inhibiting expression of a
particular gene by a variety of methods"
Biol115_2014_Lecture 11"
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Enhancer
(distal control
elements)"
Proximal
control
elements"
Transcription
start site"
DNA"
Upstream"
Exon"
Intron" Exon"
Exon"
Downstream"
Poly-A
signal"
Intron" Exon" Intron" Exon"
Cleaved
3ʹ′ end of
primary
RNA processing"
transcript"
Promoter"
Primary RNA
transcript
5ʹ′"
(pre-mRNA)"
Poly-A
Transcription
signal
sequence" termination
region"
Intron" Exon"
Transcription"
Intron RNA"
Coding segment"
mRNA"G"
P" P" P"
Start
Stop
5ʹ′ Cap" 5ʹ′ UTR" codon" codon"
Biol115_2014_Lecture 11"
AAA ⋅⋅⋅ AAA" 3ʹ′"
3ʹ′ UTR" Poly-A
tail"
11"
Promoter"
Activators"
DNA"
Enhancer"
Distal control
element"
TATA box"
DNA-
bending
protein"
Gene"
General
transcription
factors"
Group of mediator proteins"
RNA
polymerase II"
RNA
polymerase II"
Transcription
initiation complex"
Biol115_2014_Lecture 11"
RNA synthesis"
12"
The language of regulation"
Eukaryotic Regulatory elements"
Promoters"
Binding sites for
RNA polymerase"
Control elements: proximal,
distal"
Function:
enhancers,
repressors (or
suppressors)"
Biol115_2014_Lecture 11"
Bound by:
transcription
factors (called
activators or
suppressors)"
13"
Combinatorial Control of Gene
Activation"
A particular combination of control elements
can activate transcription only when the
appropriate activator proteins are present"
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Enhancer"
Control
elements"
Promoter"
Albumin gene"
LIVER CELL
NUCLEUS"
Crystallin
LENS CELL
gene"
NUCLEUS"
Available
activators"
Available
activators"
Albumin gene
expressed"
Crystallin gene
not expressed"
(a) Liver cell"
Biol115_2014_Lecture 11"
Albumin gene
not expressed"
Crystallin gene
expressed"
(b) Lens cell"
15"
Coordinately Controlled Genes
in Eukaryotes"
•  Unlike the genes of a prokaryotic operon,
each of the co-expressed eukaryotic genes
has a promoter and control elements"
•  These genes can be scattered over different
chromosomes, but each has the same
combination of control elements"
•  Copies of the activators recognise specific
control elements and promote simultaneous
transcription of the genes"
Biol115_2014_Lecture 11"
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Coordinate expression of
antimicrobial peptide genes"
chromosome 1"
Rel site"
gene 1 (cecropin)!
Rel site"
chromosome 2"
gene 2!
(diptericin)!
gene 3 !
(drosomycin)!
Rel site"
Rel is a control element that regulates the expression of antimicrobial
peptide genes"
Biol115_2014_Lecture 11"
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A program of differential gene
expression leads to the different cell
types in a multicellular organism"
•  During embryonic development, a fertilised
egg gives rise to many different cell types"
•  Cell types are organised successively into
tissues, organs, organ systems, and the whole
organism"
•  Gene expression orchestrates the
developmental programs of animals"
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•  Cell differentiation is the process by which
cells become specialised in structure and
function"
•  Differential gene expression results from
genes being regulated differently in each cell
type"
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Sequential Regulation of Gene
Expression During Cellular
Differentiation"
•  Determination commits a cell to its final fate"
•  Determination precedes differentiation"
•  Cell differentiation is marked by the production of
tissue-specific proteins"
Biol115_2014_Lecture 11"
20"
•  Myoblasts produce muscle-specific proteins and
form skeletal muscle cells "
•  MyoD is one of several “master regulatory
genes” that produce proteins that commit the
cell to becoming skeletal muscle"
•  The MyoD protein is a transcription factor that
binds to enhancers of various target genes"
Biol115_2014_Lecture 11"
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Master regulatory
gene myoD!
Nucleus"
Embryonic
precursor cell"
Other muscle-specific genes"
DNA"
OFF"
OFF"
mRNA"
OFF"
Myoblast (determined)"
MyoD protein
(transcription
factor)"
mRNA"
Part of a muscle fibre
(fully differentiated cell)"
MyoD"
mRNA"
Another
transcription
factor"
Biol115_2014_Lecture 11"
mRNA" mRNA"
Myosin, other
muscle proteins,
and cell cycle–
blocking proteins"
22"
Stem Cells of Animals
"
•  A stem cell is a relatively unspecialised cell that
can reproduce itself indefinitely and differentiate
into specialised cells of one or more types"
•  Stem cells isolated from early embryos at the
blastocyst stage are called embryonic stem cells;
these are able to differentiate into all cell types"
•  The adult body also has stem cells, which replace
non-reproducing specialised cells"
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Totipotent stem cells:
obtained from early
embryos, spores and
plant calluses – can give
rise to to a complete
individual"
"
Pluripotent stem cell:
can give rise to many
different cell types, but
cannot produce an entire
individual."
"
Multipotent stem cell:"
Gives rise to different cell
types within tissues."
Biol115_2014_Lecture 11"
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Induced
pluripotent stem
cells (iPS) can
used to treat a
repair of damaged
tissues in adults"
Biol115_2014_Lecture 11"
25"
You should now be able to:"
•  Explain the role of promoters, enhancers,
activators and repressors in transcriptional
control."
•  Explain how eukaryotic genes can be coordinately controlled."
•  Describe how cells are instructed to express
genes at the appropriate time."
•  Explain how cellular differentiation occurs at the
cellular level."
Biol115_2014_Lecture 11"
26"