Conserved properties of HP1Hsα

Laura E. Norwood, Stephanie K. Grade, Diane E. Cryderman, Karrie A. Hines, Nicholas Furiasse, Rafael Toro, Yuhong Li, Archana Dhasarathy, Michael P. Kladde, Mary J.C. Hendrix, Dawn A. Kirschmann, Lori L. Wallrath

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Heterochromatin protein 1 Hsα (HP1Hsα) is one of three human proteins that share sequence similarity with Drosophila HP1. HP1 proteins are enriched at centric heterochromatin and play a role in chromatin packaging and gene regulation. In humans, HP1Hsα is down-regulated in highly invasive/metastatic breast cancer cells, compared to poorly invasive/non-metastatic breast cancer cells. To gain insight into this differential regulation, we have cloned the HP1Hsα gene and characterized its genomic region. HP1Hsα is located on human chromosome 12q13.13, 589 bp upstream of the divergently transcribed hnRNPA1 gene. Analysis of the promoter region revealed that differential regulation of HP1Hsα between the two types of breast cancer cells is lost upon mutation of an USF/c-myc transcription factor binding site located 172 bp upstream of the predicted HP1Hsα transcription start site. These findings provide insights into the down-regulation of HP1 Hsα in highly invasive/metastatic breast cancer cells. To examine the functional properties of HP1Hsα, experiments were performed using Drosophila melanogaster as a genetic system. When human HP1 Hsα was expressed in transgenic Drosophila, silencing of reporter genes inserted at centric and telomeric locations was enhanced. Furthermore, expression of HP1Hsα rescued the lethality of homozygous Su(var)2-5 mutants lacking HP1. Taken together, these results demonstrate the participation of HP1Hsα in silent chromatin formation and that HP1Hsα is a functional homologue of Drosophila HP1.

Original languageEnglish (US)
Pages (from-to)37-46
Number of pages10
JournalGene
Volume336
Issue number1
DOIs
StatePublished - Jul 7 2004

Keywords

  • Breast cancer metastasis
  • CAF1
  • CD
  • CSD
  • Drosophila
  • EGFP
  • Gene silencing
  • HP1
  • Heterochromatin
  • base pair(s)
  • bp
  • chromatin assembly factor 1
  • chromo domain
  • chromo shadow domain
  • heterochromatin protein 1
  • kb
  • kilobase(s)
  • microgram
  • μg

ASJC Scopus subject areas

  • Genetics

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  • Cite this

    Norwood, L. E., Grade, S. K., Cryderman, D. E., Hines, K. A., Furiasse, N., Toro, R., Li, Y., Dhasarathy, A., Kladde, M. P., Hendrix, M. J. C., Kirschmann, D. A., & Wallrath, L. L. (2004). Conserved properties of HP1Hsα. Gene, 336(1), 37-46. https://doi.org/10.1016/j.gene.2004.04.003