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Histone Protein

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Histone Protein

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    1. Histone Protein By Kathy Szeniawski Harmita Modi Chad Chisolm Anhxuan Nguyen Biocomputing Spring ‘08

    2. Histone Proteins H1 H2A H2B H3 H4 Core Particle: Histone Octomer

    3. Organisms With Histones  Taxonomic Groups  +eukaryotes (4427) +animals (4324) +chordates (4320) +mammals (4318)  primates (4262)  more... (56)  more... (2)  more... (4) +fungi (65)  ascomycetes (55)  more... (10) +green plants (27)  vascular plants (17)  mosses (10)  apicomplexans (6)  kinetoplastids (5) +viruses (61) +Retroviridae (56)  Lentivirus (47)  more... (9)  Herpesviridae (4)  Bunyaviridae (1) +bacteria (12)  proteobacteria (8)  actinobacteria (4)  other sequences (5)

    4. Histone Proteins Histone Proteins package DNA into Chromosomes Over 6 feet of DNA packaged How do you package 6 feet of DNA into a chromosome?

    5. Nucleosome

    6. Histone Octamers “Beads on a String” DNA coils around Histone Octamers

    7. Nucleosome H1 binds to the Histone Octamer and the linker DNA Linker DNA links adjacent Octamers

    8. Histone Proteins 20 to 30% of the amino acids in Histone are Lysine and Arginine. Positively charged Bind to the negatively charged phosphate groups in the sugar phosphate backbone of DNA

    9. DNA Packaging Histones function to coil and uncoil DNA

    10. Uncoiled Chromatin Treated with a salt solution uncoils chromatin…Why? Na+ attaches to the phosphate groups, displaces the Histone Octamers Determining gene sequence

    11. Applications Transcription Regulation Histone methylation? Acetylated histones associate with transcriptionally active genes ex: cancer

    12. Unlocking the Histone Code Disruptions of certain histone codes are associated with abnormal pathological conditions Birth Defects Neurological Diseases Cancers Understand Mechanisms will lead to improved: Detection Therapy Prognosis of several Human diseases

    13. Secondary Structure of Yeast Histone Protein PDB # 1UHM 1 Chain Chain A 78/118 residues crystallized 1225 amino acid residues

    14. GOR4 Predicted Algorithm 3 possible alpha helices 1 possible beta strand

    15. Pele Predicted Algorithm

    16. Secondary Structure Based on NMR (protein explorer)

    17. Secondary Structure No Disulfide Bridges No Ligands No Active site No transmembrane

    18. Family

    19. Structural Motifs

    20. Phylogeny: H1 Linker Histone

    21. Rooted tree

    22. Blast P using Biology workbench ( yeast histone H1)

    23. Protein explorer VV

    24. Compare: Conserved Region

    25. Sequences alignment: boxshade

    26. Conserved region in H1 Pattern of ditribution of H1 and the carboxyl-terminal region provide insights into the evolution of H1 protein Linker are less evolutionarily conserved than core histone. However, the Linker H1 consisted of winged helices motif is well conserved. K and A residues

    27. H1 protein region Proline linked to KA alpha organization near Carboxyl terminus gives linker H1 the ability to bind to linker DNA The amino- and carboxyl-terminal domains are extremely heterogeneous in both length and amino acid component.

    28. REFERENCES Hartyl, Daniel. Jones, Elizabeth. Essential Genetics 2nd Edition. Jones and Bartlett Publishers. Sudbury, MA. 1999 Ingles, Caroline. The Histone Code 2007. Judd Rice Labs Kashinsky, Harold, John Lewis, Joel Dacks, and Juan Ausio. 2001. Origin of H1 Linker Histones. The FASEB Journal. 15. 34-42. Zhang, Yi. Reinberg, Danny. Transcription regulation by histone methylation: interplay between different covalent modifications of the core histone tails. Genes & Development. 2001. 15: 2343-2360.

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