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Eukaryotic Genomes 12 November, 2004 Text Chapter 19 Chromatin In eukaryotes, DNA is present as several different molecules. Each DNA molecule, along with its associated proteins is one chromosome. Chromosomes are in the extended conformation while they are being transcribed. They are at their most condensed during nuclear division. Eukaryotic DNA In most eukaryotes, only about 5% of the genome actually codes for protein or RNA sequence. 10 - 15% of the genome is satellite DNA, repeats of the sequence GTTAC. This DNA is mainly structural, clustering at telomeres and centromeres. About 40% of the genome is interspersed repetitive DNA, mostly from replicative transposition. 10 - 15 % of the genome is made up of introns and other transcribed spacers. 5 to 10% of the genome is regulatory sequence. About 5% of the genome is pseudogene sequence. The globin gene family arose by duplication and differentiation. Duplication can occur due to unequal crossing over. Immunoglobin genes are rearranged in immune cells to specify immune diversity. Regulation of Gene Expression Changing the level of active protein to suit cell type and environmental conditions is the goal of gene regulation. This regulation can occur at any of the steps in gene expression. Regulation of transcription is most common, important examples of each type of regulation exist. Eukaryotic genes differ form prokaryotic genes in several important respects. First, these genes are never in operons. Each is transcribed independently. Introns exist, and are spliced out of the primary transcript. Finally, control elements, the binding sites for transcription factors, may be close to or far from the promoter. How can transcription factors bound to distal control elements (activators) influence transcription? Proteins recognize specific DNA sequences by forming weak interactions between amino acids on the protein and bases in the DNA molecule. Cancer results from genetic changes that affect the cell cycle. These changes include abnormal activation of oncogenes and inactivation of tumor suppressor genes. Usually, a cancerous transformation in any cell requires that several oncogenes be activated and several tumor suppressors be inactivated. The genetic changes that cause colon cancer are well understood.