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Li e. al. (2007) Cell 128, 707 Histone Modifications in Relation to Gene Transcription HDACs Participate in Regulation of Gene Expression Histone Deacetylases HDACs Acetylation regulates gene expression HAT transcription activation complex HDAC transcription repression complex de Ruijter, A. J.; van Gennip, A. H.; Caron, H. N.; Kemp, S.; van Kuilenburg, A. B. Biochem. J. 2003, 370, 737-749. Transcription factor (regulatory protein) = protein or protein complex that enhances or inhibits transcription. III.A) Transcriptional Regulation: III.A.3) Transcription Factors exon 1 intron 1 exon 2 exon 5 exon 4 exon 3 intron 3 intron 2 intron 4 RNA transcript before editing: exon 1 exon 2 exon 4 exon 3 exon 1 exon 2 exon 3 exon 5 mRNA after editing: mRNA after editing: III.B.1) Alternative RNA Splicing Polypeptide Blueprint 1 Polypeptide Blueprint 2 III.B) Editing Gene Regulation Different exons are spliced together to givedifferent polypeptide blueprints Varies among species. Possible reason why number of human genes is so small. Examples = Amyloid Precursor Protein (APP) gene, tau proteins Is common in the human brain. III.B.1) Alternative RNA Splicing III.B) Editing Gene Regulation RNA splicing: Tau proteins University of Chicago Chuan He III.A.) Pre-translational Epigenesis See /focus/rnai/animations/animation/animation.htm for animated explanation. III.A.1) RNA Interference: Definition: A short sequence of single-strandedRNA (“iRNA”) and a complex of proteins andenzymes (“silencing stuff”) binds with mRNAand cleaves it. Result: Decreases the “dimmer switch” by reducing translation. No known human behavioral examples. Important method in neuroscience; potentialtherapeutic intervention. iRNA = Interfering Stuff = + Forms interfering complex mRNA Binds to mRNA Cleaves mRNA See /focus/rnai/animations/animation/animation.htm for animated explanation. III.A.) Pre-translational Epigenesis III.A.1) RNA Interference: /horizon/rna/ba
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