Transcriptional activation of the cyclin A gene by the architectural transcription factor HMGA2.
The HMGA2 protein belongs to the HMGA family of architectural transcription factors, which play an important role in chromatin organization. HMGA proteins are overexpressed in several experimental and human tumors and have been implicated in the process of neoplastic transformation. Hmga2 knockout results in the pygmy phenotype in mice and in a decreased growth rate of embryonic fibroblasts, thus indicating a role for HMGA2 in cell proliferation. Here we show that HMGA2 associates with the E1A-regulated transcriptional repressor p120(E4F), interfering with p120(E4F) binding to the cyclin A promoter. Ectopic expression of HMGA2 results in the activation of the cyclin A promoter and induction of the endogenous cyclin A gene. In addition, chromatin immunoprecipitation experiments show that HMGA2 associates with the cyclin A promoter only when the gene is transcriptionally activated. These data identify the cyclin A gene as a cellular target for HMGA2 and, for the first time, suggest a mechanism for HMGA2-dependent cell cycle regulation.
Tessari
Michela A
MA
Dipartimento di Biochimica, Biofisica e Chimica delle Macromolecole. Centre of Excellence in Biocristallography, University of Trieste, via L. Giorgieri 1, 34127 Trieste, Italy.
Gostissa
Monica
M
Altamura
Sandro
S
Sgarra
Riccardo
R
Rustighi
Alessandra
A
Salvagno
Clio
C
Caretti
Giuseppina
G
Imbriano
Carol
C
Mantovani
Roberto
R
Del Sal
Giannino
G
Giancotti
Vincenzo
V
Manfioletti
Guidalberto
G
D017504:Adenovirus E4 Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D016466:CHO Cells; D002453:Cell Cycle; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D006224:Cricetinae; D019925:Cyclin A / Q000235:genetics*; D018076:DNA, Complementary / Q000235:genetics; D025743:HMGA2 Protein / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008954:Models, Biological; D041681:NIH 3T3 Cells; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D016335:Zinc Fingers
D017504:Adenovirus E4 Proteins; D019925:Cyclin A; D018076:DNA, Complementary; D025743:HMGA2 Protein; D012097:Repressor Proteins; C411663:transcription factor p120(E4F)