The Cell Nucleus and the Control of Gene Expression

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CHAPTER 12

• The Cell Nucleus and the Control of Gene
  Expression

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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.

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The cell nucleus
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12.1 The Nucleus of a Eukaryotic Cell (1)

• 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
  protein-containing fibrillar network.

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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.

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The nuclear envelope
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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.

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The nuclear lamina
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The nuclear lamina
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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.

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Movement of materials though the nuclear pore
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The NPC of an amphibian oocyte
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The NPC of an amphibian oocyte
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A model of the vertebrate NPC
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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.

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Importing proteins from the cytoplasminto the
nucleus
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Importing proteins from the cytoplasminto the
nucleus (continued)
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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.

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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.

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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.

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Nucleosomal organization of chromatin
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Three-dimensional structure of a nucleosome
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Three-dimensional structure of a nucleosome
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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.

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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.

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The 30-nm fiber
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Chromatin loops
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Levels of organization of chromatin
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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 organisms life.

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The Nucleus of a Eukaryotic Cell (12)

• 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.

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X chromosome inactivation
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The Nucleus of a Eukaryotic Cell (13)

• 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.

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Histone modifications and histone code
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The Nucleus of a Eukaryotic Cell (14)

• 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.

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Example of proteins that bind selectivelyto
modified histones
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Correlation between transcriptional activityand
histone acetylation
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Model showing possible events during formation of
heterochromatin
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The Nucleus of a Eukaryotic Cell (15)

• 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.

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Human mitotic chromosomes
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Karyotypes
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The Nucleus of a Eukaryotic Cell (16)

• 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.

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Telomeres
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The Nucleus of a Eukaryotic Cell (17)

• 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.

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The role of telomerase
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The role of telomerase