BIOL 310 - Ch 21 Lecture Notes

  • what is epigenetics?

    • study of the mechanisms that produce non-heritable and heritable changes in transcriptional regulation without changes in DNA sequences

      • changing chemistry of the DNA molecule by adding methyl group without changing the bases (sequence stays the same)

  • the mechanism of epigenetics

    • DNA methylation

      • CpG islands — ~1% of human genome; 70-80% methylated

      • Histone modifications

        • the histone code — methylation & acetylation

      • DNA methylation is “normal”

        • epigenetic imprinting

        • imprinting control regions (ICR)

          • maternal allele for IGF2 is turned off and the paternal allele is turned on; size of the offspring is regulated by IGF2

        • cytosine methylation

          • methyl groups present for proteins to bind

        • steric hindrance — two things cannot exist in the same time in space

        • DNA/protein interactions

          • if the methyl groups are there and bound by methyl-CpG binding proteins transcription is downregulated

    • CpG-Met and gene expression

      • over-methylation / Beckwith-Wiedemann syndrome

        • deregulation of maternal imprinting at 11p15.5

        • over-expression of IGF2

          • individuals will have low blood sugar in babies, large body, large tongue, propensity for some cancer

      • under-methylation

        • fetal alcohol syndrome (paternally inherited)

      • “General rule”

        • increase in methylation = decrease in gene expression (vise versa)

        • methylation blocks transcription factors

    • methylome creation & maintenance

    • determining the methylome

      • bisulfide-treated DNA analysis

  • the histone code

    • histones in DNA packaging

      • nucleosomes

      • higher-order packaging

    • nucleosome

      • histone octamer

      • H2A, H2B, H3, and H4

      • H1-linker

      • N-terminus “tails” — certain tails have higher likelihood of modifications

      • 147 bp

      • 2.2 × 107 per cell

  • histones and DNA availability

    • plastic tail = protein recruitment = change in DNA affinity

    • one pattern of gene expression will differ depending on where acetylation on the histone tail occur

      • differs in subset of modifications on specific tails of histones

  • histones mods and cancer

    • H4K16Ac + H4K20Me3

      • present in many primary tumors

      • regulate higher order chromatin structure — hypothesized that histones have methylation conserved across the replication fork

    • inheriting the histone code

      • histone modification with chip-seq