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Htz-1: The story of a H2Z Histone Variant

Htz-1: The story of a H2Z Histone Variant. By Neil Bhadsavle. What is a histone?. Histones are proteins that allow DNA to be folded and compacted into smaller spaces. The negatively charged phosphate backbone of the DNA interacts with the positively charged alpha helices of histones

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Htz-1: The story of a H2Z Histone Variant

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  1. Htz-1: The story of a H2Z Histone Variant By Neil Bhadsavle

  2. What is a histone? • Histones are proteins that allow DNA to be folded and compacted into smaller spaces. • The negatively charged phosphate backbone of the DNA interacts with the positively charged alpha helices of histones • H2A is one of the six major classes of histones (H1,H2B,H3,H4,and Archaeal) are the others

  3. So what does htz-1 do? • The exact function is unknown and being debated as being a transcriptional activator or repressor (1). • Linked to temporal gene expression during foregut development in C.Elegans (1). • RNA interference has been used to confirm the results as it has lead to lethality and late foregut development(1).

  4. Htz-1 Size/Location • The Gene is 998 bp and the coding portion of the gene is 423 bp (size of mature mRNA) • There are predicted to be two exons flanking a single short intron sequence (exons are located from 1-170 and 221-473) • The gene is located on the leading strand (positive) of chromosome IV.

  5. Mutations? • There are four different alleles but only two of them have known sequence changes (tm1694 and tm2469) • Both of these mutants are just single base pair insertion or deletion mutants.

  6. tm1694 • This allele is caused by an insertion of 67 bp in the place where 645 bp were deleted. The deletion encompasses the beginning of the htz-1 gene (first 28 bp). • This allele also affects the wapl-1 gene • This mutation leads to death of larvae or sterility of the adult (according to Dr. Han of the NBP in Japan)

  7. tm2469 • tm2469 is a 345 deletion mutation right in the heart of the htz-1 gene location. • Disputed on whether fertility is affected by histone methylation on the male X chromosome.

  8. Gene Products • The htz-1 gene encodes a protein which turns out to be the histone H2A variant. (WP:CE07426 ) • This protein contains multiple motifs which include Histone Fold, Histone H2A, and Core Histone

  9. Predicted Protein structure

  10. Orthologies and Homologies • There were two orthologs of this gene in two different roundworms (C. briggsae and C. remanei) • There were multiple homologs with organisms such as D. melanogaster (fruit fly), H. sapiens (humans), S. purpuratus (sea urchin), B. Mori (silk moth), and S. cerevisiae (brewers yeast) all coding for histone H2A variants

  11. Blastx • Blastx also yielded more results on homologies do other organisms with the best hit 3e-47 and usually ranged in the e-40 to e-42 range • This included organisms such as Equus equus (horse), Gallus gallus(chicken), Mus musculus (mouse), and even Arabidopsis thaliana (plant model organism).

  12. Htz-1 and disease Htz-1 is not directly associated with any disease, but since it is a transcriptional factor and thus controls the level of transcripts formed in a gene, and thus the activity of this gene is being looked at cancer or tumor inducing cells.(2)

  13. References-Databases used • WORMBASE • PubMed (used to obtain articles for the genes) • BLAST (blastx and blastp) • PDB (Protein Data Bank) • Biology Workbench SDSC

  14. References- Papers/Websites • (1)Temporal Regulation of Foregut Development by HTZ-1/H2A.Z and PHA-4/FoxA by Dustin L. Updike and Susan E. Mango, PLOS Genetics • (2) Genome-wide dynamics of Htz1, a histone H2A variant that poises repressed/basal promoters for activation through histone loss. Cairns B.R. et al., Cell

  15. References cont. • Wikipedia articles on histones as well as other various biological information to get a better understanding.

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