Transcript CHAPTER 12

CHAPTER 12
The Cell Nucleus and the Control
of Gene Expression
Introduction
• All cells in a multicellular organism contain the
same complement of genes.
• Cells express their genetic information
selectively.
• Gene expression is controlled by regulatory
machinery in the cell nucleus.
The cell nucleus
12.1 The Nucleus of a Eukaryotic Cell
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• The contents of the nucleus are enclosed by
the nuclear envelope.
• A typical nondividing nucleus includes:
– Chromosomes as extended fibers of chromatin.
– Nucleoli for rRNA synthesis.
– Nucleoplasm as the fluid where solutes are
dissolved.
– The nuclear matrix, which is the proteincontaining fibrillar network.
The Nucleus of a Eukaryotic Cell (2)
• The Nuclear Envelope
– The nuclear envelope is a structure that divides
the nucleus from its cytoplasm.
• It consists of two membranes separated by a nuclear
space.
• The two membranes are fuses at sites forming a
nuclear pore.
• The inner surface of the nuclear envelope is lined by
the nuclear lamina.
The nuclear envelope
The Nucleus of a Eukaryotic Cell (3)
• The nuclear lamina
– Support the nuclear envelope.
– It is composed of lamins.
– The integrity of the nuclear lamina is regulated by
phosphorylation and dephosphorylation.
The nuclear lamina
The nuclear lamina
The Nucleus of a Eukaryotic Cell (4)
• The Structure of the Nuclear Pore Complex
and its Role in Nucleocytoplasmic Exchange
– Proteins and RNA are transported in and out of
the nucleus.
– Nuclear pores contain the nuclear pore complex
(NPC) that appears to fill the pore like a stopper.
– NPC is composed of ~30 proteins called
nucleoporins.
Movement of materials though the nuclear pore
The NPC of an amphibian oocyte
The NPC of an amphibian oocyte
A model of the vertebrate NPC
The Nucleus of a Eukaryotic Cell (5)
• Proteins synthesized in the cytoplasm are
targeted for the nucleus by the nuclear
localization signal (NLS).
– Proteins with an NLS stretch bind to an NLS
receptor (importin).
– Conformation of the NPC changes as the protein
passes through.
– RNAs move through the NPCs as RNPs and carry
NES (nuclear export signals) to pass through.
Importing proteins from the cytoplasm
into the nucleus
Importing proteins from the cytoplasm
into the nucleus (continued)
The Nucleus of a Eukaryotic Cell (6)
• Chromosomes and Chromatin
– Packaging the Genome
• Chromosomes consist of chromatin fibers, composed
of DNA and associated proteins.
• Each chromosome contains a single, continuous DNA
molecule.
The Nucleus of a Eukaryotic Cell (7)
• Nucleosomes: The
Lowest Level of
Chromosome
Organization
– The protein
component of
chromosomes include
histones, a group of
highly conserved
proteins.
– Histones have a high
content of basic
amino acids.
The Nucleus of a Eukaryotic Cell (8)
• DNA and histones are organized into repeating
subunits called nucleosomes.
• Each nucleosome includes a core particle of
supercoiled DNA and histone H1 serving as a
linker.
• DNA is wrapped around the core complex.
• The histone core complex consists of two
molecules each of H2A, H2B, H3, and H4
forming an octamer.
Nucleosomal organization of chromatin
Three-dimensional structure of a nucleosome
Three-dimensional structure of a nucleosome
The Nucleus of a Eukaryotic Cell (9)
• Histone
modification is
one mechanism
to alter the
character of
nucleosomes.
• DNA and histones
are held together
by noncovalent
bonds.
The Nucleus of a Eukaryotic Cell (10)
• Higher Levels of Chromatin Structure
– A 30-nm filament is another level of chromatin
packaging, maintained by histone H1.
– Chromatin filaments are organized into large
supercoiled loops.
– The presence of loops in chromatin can be seen:
• In mitotic chromosomes form which histones have
been extracted.
• In meiotic lampbrush chromosomes from amphibian
oocytes.
The 30-nm fiber
Chromatin loops
Levels of organization
of chromatin
The Nucleus of a Eukaryotic Cell (11)
• Heterochromatin and Euchromatin
– Euchromatin returns to a dispersed state after
mitosis.
– Heterochromatin is condensed during interphase.
• Constitutive heterochromatin remains condensed all
the time.
• Facultative heterochromatin is inactivated during
certain phases of the organism’s life.
The Nucleus of a Eukaryotic Cell
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• Constitutive heterochromatin :
– Found mostly around centromeres and telomeres.
– Consists of highly repeated sequences and few
genes.
• Facultative heterochromatin:
– Is found in one of the X chromosomes as a Barr
body through X inactivation.
– X inactivation is a random process, making adult
females genetic mosaics.
X chromosome inactivation
The Nucleus of a Eukaryotic Cell
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• The Histone Code and Formation of
Heterochromatin
– The histone code hypothesis states that the
activity of a chromatin region depends on the
degree of chemical modification of histone tails.
– Histone tail modifications influence chromatin in
two ways:
• Serve as docking sites to recruit nonhistone proteins.
• Alter the way in which histones of neighboring
nucleosomes interact with one another.
Histone modifications and “histone code”
The Nucleus of a Eukaryotic Cell
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• Heterochromatin has many methylated H3
histones, which stabilize the compact nature
of the chromatin.
• Small RNAs and specific enzymes play a role in
histone methylation.
Example of proteins that bind selectively
to modified histones
Correlation between transcriptional activity
and histone acetylation
Model showing possible
events during formation of
heterochromatin
The Nucleus of a Eukaryotic Cell
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• The Structure of a Mitotic Chromosome
– Chromatin of a mitotic cell exists in its most highly
condensed state.
• Staining mitotic chromosomes can provide useful
information.
• A karyotype is a preparation of homologous pairs
ordered according to size.
• The pattern on a karyotype may be used to screen
chromosomal abnormalities.
Human mitotic
chromosomes
Karyotypes
The Nucleus of a Eukaryotic Cell
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• Telomeres
– The end of each chromosome is called a telomere
and is distinguished by a set of repeated
sequences.
– New repeats are added by a telomerase, a reverse
transcriptase that synthesizes DNA from a DNA
template.
Telomeres
The Nucleus of a Eukaryotic Cell
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• Telomeres (continued)
– Telomeres are required for the complete
replication of the chromosome because they
protect the ends from being degraded.
– Telomerase activity is thought to have major
effects on cell life.
The role of telomerase
The role of telomerase