Conserved properties of HP1(Hsalpha)

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

doi:10.1016/j.gene.2004.04.003

Back

Journal article

Peer reviewed

Conserved properties of HP1(Hsalpha)

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, …

Gene, Vol.336(1), pp.37-46

07/07/2004

DOI: 10.1016/j.gene.2004.04.003

PMID: 15225874

View Online

Abstract

Heterochromatin protein 1 Hsalpha (HP1(Hsalpha)) 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, HP1(Hsalpha) 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 HP1(Hsalpha) gene and characterized its genomic region. HP1(Hsalpha) 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 HP1(Hsalpha) 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 HP1(Hsalpha) transcription start site. These findings provide insights into the down-regulation of HP1(Hsalpha) in highly invasive/metastatic breast cancer cells. To examine the functional properties of HP1(Hsalpha), experiments were performed using Drosophila melanogaster as a genetic system. When human HP1(Hsalpha) was expressed in transgenic Drosophila, silencing of reporter genes inserted at centric and telomeric locations was enhanced. Furthermore, expression of HP1(Hsalpha) rescued the lethality of homozygous Su(var)2-5 mutants lacking HP1. Taken together, these results demonstrate the participation of HP1(Hsalpha) in silent chromatin formation and that HP1(Hsalpha) is a functional homologue of Drosophila HP1.

Green Fluorescent Proteins

Humans

Gene Expression Regulation, Neoplastic

Gene Silencing

Binding Sites - genetics

Drosophila melanogaster - genetics

Promoter Regions, Genetic - genetics

Chromosomal Proteins, Non-Histone - genetics

DNA Methylation

Animals

Cell Line, Tumor

Recombinant Fusion Proteins - genetics

Adult

Female

Luminescent Proteins - genetics

Mutation

Details

Title: Subtitle: Conserved properties of HP1(Hsalpha)
Creators: Laura E Norwood - The Department of Biochemistry, The University of Iowa, 3136 MERF, Iowa City, IA 52242, USA
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
Resource Type: Journal article
Publication Details: Gene, Vol.336(1), pp.37-46
Publisher: Netherlands
DOI: 10.1016/j.gene.2004.04.003
PMID: 15225874
ISSN: 0378-1119
eISSN: 1879-0038
Grant note: GM61513 / NIGMS NIH HHS
Language: English
Date published: 07/07/2004
Academic Unit: Biochemistry and Molecular Biology; University College Courses
Record Identifier: 9984024419402771

Metrics

20 Record Views

32 Times Cited - Web of Science