Identification of the genes up- and down-regulated by the high mobility group A1 (HMGA1) proteins: Tissue specificity of the HMGA1-dependent gene regulation

Josefina Martinez Hoyos, Monica Fedele, Sabrina Battista, Francesca Pentimalli, Mogens Kruhoffer, Claudio Arra, Torben F. Orntoft, Carlo Maria Croce, Alfredo Fusco

Research output: Contribution to journalArticle

Abstract

High mobility group A (HMGA) proteins are chromatinic proteins that do not have transcriptional activity per se, however, by interacting with the transcription machinery, they regulate, negatively or positively, the expression of several genes. We searched for genes regulated by HMGA1 proteins using microarray analysis in embryonic stem (ES) cells bearing one or two disrupted hmga1 alleles. We identified 87 transcripts increased and 163 transcripts decreased of at least 4-fold in hmga1-/- ES cells. For some of them, a HMGA1-dose dependency was observed, because an intermediate level was observed in the heterozygous ES cells. When the expression analysis of these genes was extended to embryonic fibroblasts and adult tissues such as heart, spleen, and liver from hmga1-knockout mice, contrasting results were obtained. In fact, aside some genes showing the same HMGA1 regulation observed in ES cells, there were some genes that did not modify their expression, and others showing a HMGA1-mediated regulation but in an opposite direction. These results clearly indicate that HMGA1-mediated gene regulation depends on the cellular context. Finally for a couple of analyzed HMGA-regulated genes, electrophoretic mobility shift assay and chromatin immunoprecipitation revealed a direct binding of HMGA1 proteins to their promoters, suggesting a HMGA1-direct regulation of their expression.

Original languageEnglish
Pages (from-to)5728-5735
Number of pages8
JournalCancer Research
Volume64
Issue number16
DOIs
Publication statusPublished - Aug 15 2004

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Fingerprint Dive into the research topics of 'Identification of the genes up- and down-regulated by the high mobility group A1 (HMGA1) proteins: Tissue specificity of the HMGA1-dependent gene regulation'. Together they form a unique fingerprint.

  • Cite this