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Regulation of Gene Expression

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Title: Regulation of Gene Expression


1
Regulation of Gene Expression
  • CHAPTER 18

2
Bacterial 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)

3
Metabolic 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

4
Operons
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

5
Example trp operon
6
lac operon
  • repressor protein requires a small molecule
    called an inducer to make the repressor inactive
    (the repressor unblocks the path)

7
Section 18.2 Gene expression can be regulated
at any stage
8
Regulation 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

9
Structural 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

11
Regulation 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

12
DNA 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)

13
Regulation at Transcription
  • Regulation at level of transcription results in
    differential gene expression
  • Most common way that gene expression is regulated

14
Regulation 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
  1. activators bind to enhancer with 3-binding sites
  2. a DNA-bending protein brings the bound activators
    closer to the promoter
  3. 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

16
Fig. 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
17
Regulation 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

18
Fig. 18-11
Exons
DNA
Troponin T gene
Primary RNA transcript
RNA splicing
or
mRNA
19
Regulation 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

20
Fig. 18-12
Proteasome and ubiquitin to be recycled
Ubiquitin
Proteasome
Ubiquitinated protein
Protein fragments (peptides)
Protein to be degraded
Protein entering a proteasome
21
Gene 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
22
Section 18.4 A program of differential gene
expression leads to different cell types in a
multicellular organism
23
Embryonic 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
24
Cytoplasmic 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

25
Cell to Cell Signals
  • communication between cells can induce
    differentiation
  • Process is called induction

26
Determination
  • 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

27
Pattern 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

28
Identity 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?)

29
Example of a homeotic gene PAX-6
30
Section 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
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