High-mobility-group A1 (HMGA1) proteins down-regulate the expression of the recombination activating gene 2 (RAG2)

Sabrina Battista, Monica Fedele, Josefina Martinez Hoyos, Francesca Pentimalli, Giovanna Maria Pierantoni, Rosa Visone, Ivana De Martino, Carlo Maria Croce, Alfredo Fusco

Research output: Contribution to journalArticlepeer-review

Abstract

HMGA1 (high-mobility-group A1) proteins are architectural transcription factors that are found overexpressed in embryogenesis and malignant tumours. We have shown previously that they have a role in lymphopoiesis, since the loss of HMGA1 expression leads to an impairment of T-cell development and to an increase in B-cell population. Since RAGs (recombination activating genes) are key regulators of lymphoid differentiation, in the present study we investigate whether RAG2 expression is dependent on HMGA1 activity. We show that RAG2 gene expression is up-regulated in Hmga1-/- ES (embryonic stem) cells and EBs (embryoid bodies) as well as in yolk sacs and fibroblasts from Hmga1-/- mice, suggesting that HMGA1 proteins control RAG2 gene expression both in vitro and in vivo. We show that the effect of HMGA1 on RAG2 expression is direct, identify the responsible region in the RAG2 promoter and demonstrate binding to the promoter in vivo using chromatin immunoprecipitation. Since RAG2 is necessary for lymphoid cell development, our results suggest a novel mechanism by which HMGA1 might regulate lymphoid differentiation.

Original languageEnglish
Pages (from-to)91-97
Number of pages7
JournalBiochemical Journal
Volume389
Issue number1
DOIs
Publication statusPublished - Jul 1 2005

Keywords

  • Electrophoretic mobility-shift assay (EMSA)
  • Embryonic stem cell
  • High-mobility-group A1 (HMGA1)
  • Lymphopoiesis
  • MEF
  • Recombination activating gene 2 (RAG2)

ASJC Scopus subject areas

  • Biochemistry

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