1. The Cell Nucleus and the Control of Gene Expression
CHAPTER 12
The Cell Nucleus and the Control of Gene Expression

2. 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.

3. The cell nucleus

4. 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.

5. 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.

6. The nuclear envelope

7. 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.

8. The nuclear lamina

9. The nuclear lamina

10. 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.

11. Movement of materials though the nuclear pore

12. The NPC of an amphibian oocyte

13. The NPC of an amphibian oocyte

14. A model of the vertebrate NPC

15. 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.

16. Importing proteins from the cytoplasm into the nucleus

17. Importing proteins from the cytoplasm into the nucleus (continued)

18. 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.

19. 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.

20. 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.

21. Nucleosomal organization of chromatin

22. Three-dimensional structure of a nucleosome

23. Three-dimensional structure of a nucleosome

24. 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.

25. 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.

26. The 30-nm fiber

27. Chromatin loops

28. Levels of organization of chromatin

29. 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.

30. 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.

31. X chromosome inactivation

32. 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.

33. Histone modifications and “histone code”

34. 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.

35. Example of proteins that bind selectively to modified histones

36. Correlation between transcriptional activity and histone acetylation

37. Model showing possible events during formation of heterochromatin

38. 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.

39. Human mitotic chromosomes

40. Karyotypes

41. 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.

42. Telomeres

43. 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.

44. The role of telomerase

45. The role of telomerase