Title: Regulation of Gene Expression
1Regulation of Gene Expression
2Bacterial Genome Replication
Section 18.1 Bacteria can respond to
environmental change by regulating gene
transcription
- double-stranded, circular DNA located in the
nucleoid region - many bacteria also have plasmids smaller
circles of DNA with a few genes - reproduce by binary fission
- therefore, most bacteria in a colony are
genetically identical - genetic diversity can arise as a result of
mutation especially when reproductive rates are
high (short generation spans)
3Metabolic Control in Bacteria
- adjust the activity of enzymes already present
via chemical cues - (ex) feedback inhibition
- adjust the amount of enzyme being made by
regulating gene expression - basic mechanism is described in the operon model
4Operons
operator
gene A
gene B
gene C
gene D
promoter
- made up of an operator, promoter, a set of
functionally related genes - operator segment of DNA that acts like an
on/off switch for transcription positioned w/in
promoter or between promoter genes - promoter site where RNA polymerase binds to DNA
begins transcription - set of genes transcription unit
5Example trp operon
6lac operon
- repressor protein requires a small molecule
called an inducer to make the repressor inactive
(the repressor unblocks the path)
7Section 18.2 Gene expression can be regulated
at any stage
8Regulation at Structural Levels of DNA
- a single linear DNA double helix averages about 4
cm in length - DNA associates with proteins that condense it so
it will fit in the nucleus - DNA-protein complex chromatin
- chromatin looks like beads on a string when
unfolded - beads nucleosomes made up of histones
(proteins) - string DNA
9Structural Levels of DNA
10- chromatin fiber (30 nm)
- created by interactions between adjacent
nucleosomes and the linker DNA - chromatin fiber (300 nm)
- created when the 30 nm chromatin fiber forms
loops called looped domains attached to a protein
scaffold made of nonhistones - chromosome
- forms when the 300 nm chromatin fiber folds on
itself
11Regulation of Chromatin Structure
- compactness of chromatin helps regulate gene
expression - heterochromatin highly compact so it is
inaccessible to transcription enzymes - euchromatin less compact allowing transcription
enzymes access to DNA - chemical modifications that can alter chromatin
compactness - histone acetylation (-COCH3) neutralizes the
histones so they no longer bind to neighboring
nucleosomes causing chromatin to have a looser
structure
12DNA Methylation
- addition of methyl groups to DNA bases (usually
cytosine) inactivates DNA - methylation patterns can be passed on
- after DNA replication, methylation enzymes
correctly methylate the daughter strand - accounts for genomic imprinting in mammals
expression of either the maternal or paternal
allele of certain genes during development - (NOTE inheritance of chromatin modifications
that do not involve a change in the DNA sequence
is called epigenetic inheritance)
13Regulation at Transcription
- Regulation at level of transcription results in
differential gene expression - Most common way that gene expression is regulated
14Regulation of Transcription Initiation
- general transcription factors proteins that
form a transcription initiation complex on the
promoter sequence (ex TATA box) allowing RNA
polymerase to begin transcription - control elements segments of noncoding DNA that
help regulate transcription by binding certain
proteins - proximal control elements
- distal control elements (enhancers) - interact
with specific transcription factors - activators stimulate transcription by binding to
enhancers - repressors - inhibit transcription by binding
directly to enhancers or by blocking activator
binding to enhancers or other transcription
machinery
15- activators bind to enhancer with 3-binding sites
- a DNA-bending protein brings the bound activators
closer to the promoter - activators bind to general transcription factors
mediator proteins, helping them to form a
functional transcription initiation complex
- activators can also promote histone acetylation
repressors can promote histone deacetylation
16Fig. 18-10
Enhancer
Promoter
Albumin gene
Control elements
Crystallin gene
LENS CELL NUCLEUS
LIVER CELL NUCLEUS
Available activators
Available activators
Albumin gene not expressed
Albumin gene expressed
Crystallin gene not expressed
Crystallin gene expressed
(b) Lens cell
(a) Liver cell
17Regulation of RNA splicing
- In alternative RNA splicing, different mRNA
molecules are produced from the same primary
transcript, depending on which RNA segments are
treated as exons and which as introns
18Fig. 18-11
Exons
DNA
Troponin T gene
Primary RNA transcript
RNA splicing
or
mRNA
19Regulation of Protein Lifespan
- After translation, various types of protein
processing, including cleavage and the addition
of chemical groups, are subject to control - Proteasomes are giant protein complexes that bind
protein molecules and degrade them
20Fig. 18-12
Proteasome and ubiquitin to be recycled
Ubiquitin
Proteasome
Ubiquitinated protein
Protein fragments (peptides)
Protein to be degraded
Protein entering a proteasome
21Gene Regulation
7
6
protein processing degradation
1 2. transcription - DNA packing -
transcription factors 3 4. post-transcription
- mRNA processing - splicing - 5 cap
poly-A tail - breakdown by siRNA 5.
translation - block start of translation 6
7. post-translation - protein processing -
protein degradation
5
4
initiation of translation
mRNAprocessing
2
1
initiation of transcription
mRNA protection
4
mRNA splicing
3
22Section 18.4 A program of differential gene
expression leads to different cell types in a
multicellular organism
23Embryonic Development
- Zygote transforms as a result of 3 processes
- cell division
- Number of cells increases through mitosis
- cell differentiation
- process by which cells become specialized in
structure function - morphogenesis
- Organization of cells into tissues and organs
Cell differentiation arises primarily from
differences in gene expression not from
differences in the cells genomes -
Differentiation and morphogenesis are controlled
by both cytoplasmic determinants and cell to cell
signals
24Cytoplasmic Determinants
- maternal substances in the egg that influence the
course of early development - distributed unevenly to new cells produced by
mitotic division of the zygote - the set of cytoplasmic determinants a cell
receives helps regulate gene expression
25Cell to Cell Signals
- communication between cells can induce
differentiation - Process is called induction
26Determination
- the events that lead to the observable
differentiation of a cell - at the end of this process, an embryonic cell is
irreversibly committed to its final fate
(determined) - marked by the expression of genes for tissue
specific proteins, which act as transcription
factors for genes that help define cell type
27Pattern Formation
- development of a spatial organization in which
the tissues and organs of an organism are all in
their characteristic places - begins in early embryo when the major axes of the
organism are established - molecular cues (positional information) that
control pattern formation are provided by
cytoplasmic determinants inductive signals
28Identity of Body Parts
- controlled by homeotic genes
- turned on by segment-polarity gene products
- specify the types of appendages and other
structures that each segment will form - (why are homeotic genes found in clusters?)
29Example of a homeotic gene PAX-6
30Section 18.5 Cancer results from genetic
changes that affect cell cycle control
- The gene regulation systems that go wrong during
cancer are the very same systems involved in
embryonic development - Cancer can be caused by mutations to genes that
regulate cell growth and division - Tumor viruses can cause cancer in animals
including humans
- Oncogenes are cancer-causing genes
- Proto-oncogenes are the corresponding normal
cellular genes that are responsible for normal
cell growth and division