Chapter 19: Eukaryotic Genomes Most gene expression regulated through transcription/chromatin structure Most gene expression regulated through transcription/chromatin structure Histones (+ proteins) bind to – DNA Histones (+ proteins) bind to – DNA Nucleosome- DNA wound around histones separated by linker DNA strands Nucleosome- DNA wound around histones separated by linker DNA strands Telomere & centromere regions=heterochromatin  inaccessible to polymerases Telomere & centromere regions=heterochromatin  inaccessible to polymerases Differential gene expression  cell specialization Differential gene expression  cell specialization

Gene expression control: regulation of chromatin structure Heterochromatin never expressed Heterochromatin never expressed Expression of genes through chemical modifications of histones Expression of genes through chemical modifications of histones Histone acetylation: Histone acetylation: (-COCH 3 ) is attached to + histone tail (-COCH 3 ) is attached to + histone tail Histone tail is neutralized Histone tail is neutralized histone no longer binds histone no longer binds Allows polymerases gene access Allows polymerases gene access De-acetylation allows recoiling of histone De-acetylation allows recoiling of histone

DNA methylation DNA methylation Methyl groups added to cytosine  inactivate gene expression inactivated long term Methyl groups added to cytosine  inactivate gene expression inactivated long term Methylation pattern passed through genomic imprinting Methylation pattern passed through genomic imprinting

Gene expression control: regulating transcription initiation General transcription factors  assembly of transcription initiation complex (low rate of transcription) General transcription factors  assembly of transcription initiation complex (low rate of transcription) specific transcription factors  affect transcription rate specific transcription factors  affect transcription rate Activators- binds to enhancer  stimulate transcription Activators- binds to enhancer  stimulate transcription Repressors- inhibit expression by Repressors- inhibit expression by preventing activator binding preventing activator binding Inhibiting the enhancer Inhibiting the enhancer

Gene expression control: Post- transcriptional regulation RNA processing RNA processing Alternative RNA splicing Alternative RNA splicing Segments of primary transcript treated as exons & introns varies Segments of primary transcript treated as exons & introns varies regulatory proteins determine intron-exon choices regulatory proteins determine intron-exon choices mRNA degradation mRNA degradation Enzymes degrade mRNA by Enzymes degrade mRNA by shortening poly-A tail shortening poly-A tail removing 5’ cap removing 5’ cap Nuclease destroys the mRNA Nuclease destroys the mRNA microRNAs bind to complementary mRNA sequence microRNAs bind to complementary mRNA sequence dicer enzyme cuts this double stranded RNA dicer enzyme cuts this double stranded RNA RNA interference (RNAi) RNA interference (RNAi)

Gene expression control: Post- transcriptional regulation Blocking translation initiation Blocking translation initiation Regulatory proteins block ribosome attachment Regulatory proteins block ribosome attachment Environmental factors regulate initiation factors Environmental factors regulate initiation factors Protein processing & degradation Protein processing & degradation Delay of protein modification/activation Delay of protein modification/activation Enzymes destroy protein Enzymes destroy protein

Eukaryotic Genomes: non-coding DNA sequences Non-coding regions Non-coding regions “junk DNA” “junk DNA” Code for rRNA & tRNA Code for rRNA & tRNA Repetitive DNA Repetitive DNA Sequences with multiple copies in the genome Sequences with multiple copies in the genome Mostly transposable elements Mostly transposable elements Transposable Elements Transposable Elements Transposons Transposons Move within genome Move within genome “cut & paste” “cut & paste” Retro-transposons Retro-transposons Move within the genome Move within the genome ” copy & paste” ” copy & paste”

Repetitive DNA Repetitive DNA Repeated sequences of 15 to 500 nucleotides Repeated sequences of 15 to 500 nucleotides The number of times the repeat occurs varies The number of times the repeat occurs varies Often found at centromeres & telomeres Often found at centromeres & telomeres

Genes & Multi-gene families Multi-gene families Multi-gene families Identical or very similar genes Identical or very similar genes Identical genes = histone proteins or RNA Identical genes = histone proteins or RNA Non-identical genes code for families of proteins (ex. Globins  myoglobin and hemoglobin) Non-identical genes code for families of proteins (ex. Globins  myoglobin and hemoglobin)

Genome Evolution Evolution occurs through Evolution occurs through Duplications Duplications Failure during meiosis ex. Polyploidy, unequal crossing over, slippage Failure during meiosis ex. Polyploidy, unequal crossing over, slippage Example: globin genes Example: globin genes Rearrangements Rearrangements Exon duplication Exon duplication Exon shuffling Exon shuffling Transposable elements Transposable elements mutations mutations