High-mobility-group A1 (HMGA1) proteins down-regulate the expression of the recombination activating gene 2 (RAG2).
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.
Battista
Sabrina
S
Dipartimento di Biologia e Patologia Cellulare e Molecolare, Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Facoltà di Medicina e Chirurgia, Università degli Studi di Napoli Federico II, via Pansini, 5, 80131 Naples, Italy.
Fedele
Monica
M
Martinez Hoyos
Josefina
J
Pentimalli
Francesca
F
Pierantoni
Giovanna Maria
GM
Visone
Rosa
R
De Martino
Ivana
I
Croce
Carlo Maria
CM
Fusco
Alfredo
A
D000818:Animals; D001665:Binding Sites; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics*; D015536:Down-Regulation; D005347:Fibroblasts / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D024003:HMGA Proteins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D013234:Stem Cells / Q000378:metabolism; D015854:Up-Regulation; D015017:Yolk Sac / Q000378:metabolism
D022782:CCAAT-Enhancer-Binding Protein-beta; D004268:DNA-Binding Proteins; D024003:HMGA Proteins; C064655:V(D)J recombination activating protein 2