Gene Expression and Chromosome Structure Quiz

Eukaryotic Genomes: Organization & Regulation

• Eukaryotic and prokaryotic cells both contain double-stranded DNA, but their genomes are organized differently.
• Prokaryotic DNA is usually circular, much smaller, associated with few proteins, and less elaborately structured than eukaryotic DNA, which is complexed with a large amount of protein to form chromatin.
• Eukaryotic DNA is highly extended during interphase and condensed into chromosomes during mitosis, whereas prokaryotic DNA is a small nucleoid region only visible with an electron microscope.

Chromatin Structure

• Chromatin structure is based on successive levels of DNA packing.
• The first level, nucleosomes, or "beads on a string," involves DNA wrapped around histone proteins (H2A, H2B, H3, H4). A fifth histone (H1) attaches near the bead during further packing.
• The next level forms a 30-nm chromatin fiber.
• Looped domains are made up of the 30-nm fiber attached to a nonhistone protein scaffold, resulting in a 300-nm fiber.
• Ultimately, these looped domains coil and fold to form the characteristic metaphase chromosome structure in mitotic chromosomes.
• In interphase cells, most chromatin is in a highly extended form, called euchromatin, which is less condensed than mitotic chromatin.

Nucleosomes

• Histones, small proteins rich in basic amino acids (arginine and lysine), bind tightly to the negatively charged DNA.
• They are present in approximately equal amounts to DNA in eukaryotic cells, and are evolutionarily conserved.
• Histones are responsible for the first level of DNA packing in chromatin.
• The association of DNA and histones seems to remain intact throughout the cell cycle.

Higher Levels of DNA Packing

• 10-nm fiber: Nucleosomes (beads) on a string are formed by the DNA wrapping around histones.
• 30-nm fiber: Nucleosomes are further packaged, forming a condensed 30-nm fiber.
• 300-nm fiber: Looped domains are formed where 30-nm fibers are attached to a protein scaffold.
• Metaphase chromosomes: These looped domains coil and fold further to produce compact metaphase chromosomes.

Gene Expression Regulation

• Gene expression can be regulated at any stage, but transcription is the key step.
• Different organisms and cells have different gene expression needs and they must turn on/off genes as needed.
• During development, cells undergo specialization called cell differentiation. Gene expression needs to be regulated in these cells too.
• Gene regulation is important for multicellular organisms and in medical as well as basic biological research.
• Portions of chromosomes remain highly condensed throughout the cell cycle, even during interphase, forming heterochromatin. Heterocromatin is not transcribed, while euchromatin is.
• Cell differentiation requires regulated gene expression.

Differential Gene Expression

• Each cell in a multi-cellular eukaryote expresses only a fraction of its genes.
• In each different cell type, a unique subset of genes is expressed.

Chromatid Modifications of Regulation

• Chromatin modifications affect gene availability for transcription.
• Genes within highly condensed heterochromatin are usually not expressed.
• Chemical modifications of histone tails can affect chromatin configuration and thus gene expression.
• Histone acetylation seems to loosen chromatin structure enhancing transcription.

DNA Methylation

• Adding methyl groups to certain bases in DNA is associated with reduced transcription in some species.

Transcription Initiation

• Transcription initiation is controlled by proteins that interact with DNA and each other.
• Chromatin-modifying enzymes provide initial control over gene expression, by either increasing or decreasing the availability of DNA to transcription machinery.

The Roles of Transcription Factors

• Eukaryotic RNA polymerase requires transcription factors to initiate transcription.
• Transcription factors can be activators or repressors which control expression.

Enhancers and Specific Transcription Factors

• Proximal control elements are located near the promoter.
• Distal control elements, called enhancers, may be far away from a gene or even in an intron.
• Specific transcription factors function as repressors by inhibiting the expression of certain genes.
• Some activators are located far away and act by influencing chromatin structure.

Coordinately Controlled Genes

• Coordinately controlled genes share regulatory sites and may be grouped to form operons in prokaryotes but not in eukaryotes.
• Even with the genes spread on different chromosomes, coordinated expression can occur through regulatory DNA sequences or enhancers regulated by a type of transcription factor that affects a group of genes simulataneously.

Post-Transcriptional Regulation

• An increasing number of regulatory mechanisms operate after transcription, supporting gene expression.

RNA Processing

• Alternative RNA splicing produces different mRNA molecules from one primary transcript.

mRNA Degradation

• The length of mRNA molecules in the cytoplasm determines protein synthesis rates. mRNA stability is determined by sequences in the 5' leader and 3' trailer regions.

RNA Interference (miRNA)

• miRNA can regulate gene expression by either degrading mRNA or blocking its translation.

Initiation of Translation

• The initiation of translation can be blocked by regulatory proteins attaching to specific mRNA sequences or structures, or controlled through the regulation of all mRNAs in a cell.

Protein Processing and Degradation

• After translation, various protein processing activities, like cleavage and chemical modifications, are regulated.
• Giant protein complexes called proteasomes bind and degrade protein molecules.

Cancer

• Cancer results from genetic changes that affect cell cycle control.
• Genes involved in the cell cycle (proto-oncogenes and tumor suppressor genes), need to be regulated properly, and changes in these regulations can cause cancer.
• The gene regulation systems involved in embryonic development are also involved in cell cycle regulation.
• Uncontrolled cell division is caused by proto-oncogenes turning into oncogenes that promote cell division uncontrollably.
• Tumor suppressor genes regulate cell growth and inhibit division, and when these are affected it can cause uncontrollably growth leading to cancer.

Multistep Model of Cancer Development

• Cancer cells arise through several steps.
• Accumulation of multiple mutations affecting proto-oncogenes and tumor suppressor genes is needed to change a normal cell into cancer cells
• Certain viruses promote cancer by integrating viral DNA into a cell's genome.

Inherited Predisposition to Cancer

• Individuals who inherit a mutated oncogene or tumor-suppressor allele have a higher risk of developing certain cancers.