Chapter 12 - Regulation of Transcription in Eukaryotes

• Transcription factors and DNA enhancer elements control the transcription of individual genes.
• The machinery required for generating the distinct patterns of gene transcription that occur in eukaryotic cells has many components, including trans-acting regulatory proteins and cis-acting regulatory DNA sequences.
• The regulatory proteins can be divided into two sets, those that directly bind DNA and those that do not.
• The first set of regulatory proteins consists of transcription factors that directly bind regulatory DNA sequences called enhancers.
• Enhancers that are located close to the core promoter are part of proximal promoters and are called proximal enhancers, and those that are a considerable distance from the promoter are part of distal enhancers and are called enhancers.
• Some general transcription factors (GTFs) directly bind DNA regulatory sequences within core promoters that surround transcription start sites.
• The second set of regulatory proteins consists of coregulators, which do not directly bind DNA.
• Newly formed cells inherit both genetic information, inherent in the nucleotide sequence of DNA, and epigenetic information, built into histone and DNA modifications.
• Cellular memory, position-effect variegation, genomic imprinting, and X-chromosome inactivation are examples of epigenetic phenomenon where the transcription state of single genes, multiple genes, and even whole chromosomes is inherited without changing the sequence of DNA.
• Thus, the nucleotide sequence of genomes is not sufficient for understanding the inheritance of normal and disease states of transcription.
• There are two types of coregulators: coactivators and corepressors.
• Coactivators and corepressors, respectively, increase or decrease the amount of transcription through binding or enzymatically modifying other transcription regulatory factors.
• Distal and proximal enhancers are DNA sequences that regulate the transcription of genes.
• Coregulators, which bind transcription factors, control the recruitment and access to DNA of general transcription factors and RNA polymerase II.
• Saccharomyces cerevisiae, or budding yeast, is a premier eukaryotic genetic system.
• Writers, erasers, and chromatin remodelers, which all repress transcription, are in a complex with or temporarily associate with readers.
• Histone and DNA modifications are added and removed and histone DNA interactions are changed.
• Cellular memory, position-effect variegation, genomic imprinting, and X-chromosome inactivation are examples of the epigenetic control of transcription.
• Information stored in the structure of chromatin is inherited through cell divisions, a process known as epigenetic inheritance.
• Epigenetic inheritance affects the traits of daughter cells without altering DNA sequence.
• Polycomb group proteins and Trithorax group proteins maintain the cellular memory of transcription in Drosophila.
• Polycomb and Trithorax proteins often function in opposition, with Polycomb proteins maintaining genes in a transcriptionally repressed state and Trithorax proteins maintaining genes in a transcriptionally active state.
• In position-effect variegation, the expression of genes can be silenced when they are experimentally relocated to another region of a chromosome.
• Yeast has a very compact genome with only about 12 megabase pairs of DNA (compared with almost 3000 megabase pairs for humans) containing approximately 6000 genes that are distributed on 16 chromosomes.
• Yeast was the first eukaryote to have its genome sequenced.
• In both cases, the mother cell produces a bud containing an identical daughter cell.
• Diploid cells either continue to grow by budding or are induced to undergo meiosis, which produces four haploid spores held together in an ascus (also called a tetrad).
• Spores of the same mating type will continue growth by budding.
• Yeast has been called the E. coli of eukaryotes because of the ease of forward and reverse mutant analysis.
• CD and CSD indicate the HP1 chromodomain and chromoshadow domain, respectively, and purple circles indicate nucleosomes.
• In the absence of any barriers, heterochromatin might spread into adjoining regions and inactivate genes in some cells but not in others.
• The spreading of heterochromatin into active gene regions could be disastrous for an organism because active genes would be silenced as they are converted into heterochromatin.
• Boundary/insulator elements prevent the spreading of heterochromatin by creating a local environment that is not favorable to heterochromatin formation.
• Proteins involved in the spread of heterochromatin include writers, readers, and erasers of histone modifications.
• The phenomenon of genomic imprinting was discovered about 35 years ago in mammals.
• In genomic imprinting, certain autosomal genes are expressed in a parent-of-origin-specific manner.
• Conversely, H19 transcripts come exclusively from the mother’s allele; H19 is an example of paternal imprinting because the paternal copy is transcriptionally inactive.
• The consequence of parental imprinting is that imprinted genes are expressed as if only one copy of the gene is present in the cell even though there are two.
• Imprinted genes are controlled by DNA regulatory elements called imprinting control regions (ICRs) that have parent-specific chromatin modifications.
• In the mouse Igf2 and H19 genes, the ICR DNA that lies between the two genes is methylated in male germ cells and unmethylated in female germ cells.