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.
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Research Article|
June 21 2005
High-mobility-group A1 (HMGA1) proteins down-regulate the expression of the recombination activating gene 2 (RAG2)
Sabrina BATTISTA;
Sabrina BATTISTA
*Dipartimento di Biologia e Patologia Cellulare e Molecolare e/o Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Facoltà di Medicina e Chirurgia di Napoli, Università degli Studi di Napoli ‘Federico II’, via Pansini, 5, 80131 Naples, Italy
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Monica FEDELE;
Monica FEDELE
*Dipartimento di Biologia e Patologia Cellulare e Molecolare e/o Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Facoltà di Medicina e Chirurgia di Napoli, Università degli Studi di Napoli ‘Federico II’, via Pansini, 5, 80131 Naples, Italy
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Josefina Martinez HOYOS;
Josefina Martinez HOYOS
*Dipartimento di Biologia e Patologia Cellulare e Molecolare e/o Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Facoltà di Medicina e Chirurgia di Napoli, Università degli Studi di Napoli ‘Federico II’, via Pansini, 5, 80131 Naples, Italy
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Francesca PENTIMALLI;
Francesca PENTIMALLI
*Dipartimento di Biologia e Patologia Cellulare e Molecolare e/o Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Facoltà di Medicina e Chirurgia di Napoli, Università degli Studi di Napoli ‘Federico II’, via Pansini, 5, 80131 Naples, Italy
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Giovanna Maria PIERANTONI;
Giovanna Maria PIERANTONI
*Dipartimento di Biologia e Patologia Cellulare e Molecolare e/o Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Facoltà di Medicina e Chirurgia di Napoli, Università degli Studi di Napoli ‘Federico II’, via Pansini, 5, 80131 Naples, Italy
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Rosa VISONE;
Rosa VISONE
*Dipartimento di Biologia e Patologia Cellulare e Molecolare e/o Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Facoltà di Medicina e Chirurgia di Napoli, Università degli Studi di Napoli ‘Federico II’, via Pansini, 5, 80131 Naples, Italy
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Ivana De MARTINO;
Ivana De MARTINO
*Dipartimento di Biologia e Patologia Cellulare e Molecolare e/o Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Facoltà di Medicina e Chirurgia di Napoli, Università degli Studi di Napoli ‘Federico II’, via Pansini, 5, 80131 Naples, Italy
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Carlo Maria CROCE;
Carlo Maria CROCE
†Kimmel Cancer Center, Thomas Jefferson University, 233 S 10th Street, Philadelphia, PA 19107, U.S.A.
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Alfredo FUSCO
Alfredo FUSCO
1
*Dipartimento di Biologia e Patologia Cellulare e Molecolare e/o Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Facoltà di Medicina e Chirurgia di Napoli, Università degli Studi di Napoli ‘Federico II’, via Pansini, 5, 80131 Naples, Italy
‡NOGEC (Naples Oncogenomic Center)–CEINGE, Biotecnologie Avanzate, via Comunale Margherita 482, 80145, Naples, Italy
1To whom correspondence should be addressed, at Dipartimento di Biologia e Patologia Cellulare e Molecolare (email afusco@napoli.com).
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Publisher: Portland Press Ltd
Received:
September 20 2004
Revision Received:
January 25 2005
Accepted:
February 14 2005
Accepted Manuscript online:
February 16 2005
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London
2005
Biochem J (2005) 389 (1): 91–97.
Article history
Received:
September 20 2004
Revision Received:
January 25 2005
Accepted:
February 14 2005
Accepted Manuscript online:
February 16 2005
Citation
Sabrina BATTISTA, Monica FEDELE, Josefina Martinez HOYOS, Francesca PENTIMALLI, Giovanna Maria PIERANTONI, Rosa VISONE, Ivana De MARTINO, Carlo Maria CROCE, Alfredo FUSCO; High-mobility-group A1 (HMGA1) proteins down-regulate the expression of the recombination activating gene 2 (RAG2). Biochem J 1 July 2005; 389 (1): 91–97. doi: https://doi.org/10.1042/BJ20041607
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