Eukaryotic Cell Nucleus

• Eukaryotic cells are defined by the nucleus which houses genetic material.
• The nucleus has a double membrane, made of two lipid bilayers.
• The nuclear membrane communicates with the cytoplasm via nuclear pores.
• DNA in eukaryotic cells exists as chromatin, a complex of histones and other proteins.
• Chromatin's structure changes based on a cell's needs, it is a dynamic structure.
• Histone modification regulates chromatin structure, thus impacting gene expression.
• The nucleus is the most apparent internal structure of a cell, and is a defining characteristic.
• DNA is held inside a double membrane structure that connects to the endoplasmic reticulum.
• The fibrous nuclear lamina bolsters the nuclear membrane, providing structural support.
• The nucleus contains subdomains that can assemble or disassemble as required.
• The nucleolus is the best understood subdomain of the nucleus, this is where ribosome assembly occurs.
• The nuclear membrane's double bilayer presents a barrier to movement of materials between the nucleus and cytoplasm.
• Nuclear pores regulate transport between the nucleus and cytoplasm.
• A nuclear complex contains ~30 proteins (nucleoporins) that span the double membrane.
• Small ions and molecules under 5 kilodaltons can freely diffuse through the pores.
• Proteins smaller than 60 kilodaltons can pass through the pores via passive diffusion, but slower.
• Larger macromolecules and protein complexes use active transport through nuclear pores.
• Progeria, also known as Hutchinson-Gilford progeria syndrome, is a genetic condition which causes premature aging.
• Progeria is caused by a point mutation in the lamin A protein, which is normally found in the nuclear lamina.
• The mutation in Progeria prevents lamin A incorporation into the lamina, making structural support for the membrane weaker.
• Progeria also prevents normal chromatin organization, which impairs cell division.

Chromatin and Chromosomal Structure

• The DNA in a eukaryotic cell's nucleus divides into chromosomes.
• Each chromosome is a very long, single DNA strand.
• A bacterial chromosome (E. coli) has a circular shape and measures ~1 mm.
• An E. coli cell has a length of ~2 µm.
• A human genome is ~2 m and comprises 46 linear chromosomes.
• A human cell nucleus is ~5 µm in diameter.
• Consisting of a single, long DNA strand combined with various RNA and protein molecules, each chromosome is a component of chromatin.
• Chromatin's structure compacts linear DNA molecules for fitting inside the nucleus.
• Gene expression, DNA replication, and cell division are regulated by chromatin in its highly dynamic structure.
• The nucleosome is the basic chromatin unit, there are ~150 DNA nucleotides wound around a histone protein core.
• The histone core is composed of two copies each of 4 different histones (H2A, H2B, H3, H4).
• If entirely stretched, nucleosomes give the appearance of "beads on a string".
• Between the "beads" is a linker DNA short stretch that ranges from a few to ~80 nucleotides such that the nucleosome structure repeats on average approx. every 200 nucleotides.
• During interphase (when cells are not actively dividing) the chromatin condenses into a ~30 nm diameter fiber.
• The real packaging structure of the 30 nm fiber is not known.
• Interactions between the N-terminal tails of histones in neighboring nucleosomes are important to form the 30 nm fiber.
• Linker histone H1 adheres to the outside of each nucleosome and helps condense chromatin.
• Interphase chromatin is not homogenous, but it is composed of at least two types.
• Heterochromatin is highly condensed and resists gene expression ("silenced").
• Heterochromatin includes specialized structures like centromeres and telomeres.
• Euchromatin is less condensed and accessible to the RNA transcription machinery.
• Chromatin structured can be regulated by covalent modifications to the histone tails.
• 30 nm fibers require further condensation to properly fit into a nucleus.
• This requires extensive looping and interactions with non-histone proteins, including the nuclear lamina.
• Mitotic chromosomes represent chromatin's most highly condensed form.
• Within each chromosome are specialized sequences required for proper duplication.
• A replication origin is where DNA duplication begins, and eukaryotic chromosomes usually have many to make duplication faster.
• The centromere is where the mitotic spindle attaches, allowing each duplicated chromosome copy to be pulled into each daughter cell during mitosis.
• Telomeres prevent chromosome ends from being mistaken as broken DNA, while allowing for proper chromosome end duplication.

Eukaryotic cells are defined by their nucleus, which houses genetic material within a double membrane. This nuclear membrane, a double lipid bilayer, communicates with the cytoplasm through nuclear pores. DNA exists as chromatin, a dynamic complex of histones and proteins that regulates gene expression.