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 (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.

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 cytoplasminto the nucleus

Importing proteins from the cytoplasminto 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 (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.

X chromosome inactivation

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.

Histone modifications and “histone code”

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.

Example of proteins that bind selectivelyto modified histones

Correlation between transcriptional activityand histone acetylation

Model showing possible events during formation of

heterochromatin

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.

Human mitotic chromosomes

Karyotypes

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.

Telomeres

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.

The role of telomerase

The role of telomerase