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Chromosomal binding sites of the homeotic cofactor Homothorax

Lior Cohen1, Adi Salzberg

  • 1Department of Genetics and the Rappaport Family Institute for Research in the Medical Sciences, Faculty of Medicine, Technion-Israel Institute of Technology, P.O. Box 9649, Haifa, 31096, Israel.

Molecular Genetics and Genomics : MGG
|May 16, 2008
PubMed

Insights

The homothorax (hth) gene in fruit flies directly regulates about 150 genes, influencing cell growth and development. Hth

Area of Science:

  • Developmental Biology
  • Genetics
  • Molecular Biology

Background:

  • Meis family oncoproteins are vital in leukemogenesis and cancer.
  • Meis proteins' transforming potential relies on gene activation, necessitating target gene identification.
  • The fruit fly's homothorax (hth) gene, a Meis homolog, is crucial for development but its direct transcriptional targets are unknown.

Purpose of the Study:

  • To identify direct transcriptional target genes regulated by the homothorax (hth) protein.
  • To investigate the chromosomal distribution and nature of Hth binding sites in vivo.
  • To explore Hth's role in hormone-induced gene expression and its impact on cell growth.

Main Methods:

  • Chromatin immunoprecipitation (ChIP) on polytene chromosomes from Drosophila melanogaster salivary glands.
  • Cytological mapping of Hth in vivo binding sites.
  • Analysis of Hth's role in salivary gland cell size and DNA content.

Main Results:

  • Hth binds to approximately 150 reproducible sites on polytene chromosomes in salivary glands.
  • Over 100 Hth binding sites were mapped cytologically.
  • Hth accumulates at hormone-induced chromosomal puffs, suggesting a role in ecdysone-regulated gene activation.
  • Disrupting Hth activity reduces salivary gland cell size and DNA content.

Conclusions:

  • Hth directly regulates a significant number of genes, identified through its binding sites on polytene chromosomes.
  • Hth appears to play a role in the transcriptional regulation of ecdysone-induced genes.
  • Hth is implicated in regulating cell growth and endoreplication in Drosophila larval salivary glands.

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