HOXB7 expression is regulated by the transcription factors NF-Y, YY1, Sp1 and USF-1.
Products of HOX genes are transcription factors responsible for developmental regulation and postnatal tissue homeostasis. Besides their well-established function played during embryonic development, we had previously demonstrated the direct role of HOXB7 in tumor progression through transactivation of several genes involved in the proliferative and angiogenic processes. This role is at first exerted through the deregulated, constitutive expression of this gene. To define the factors possibly responsible for such activation, we studied the molecular regulation of HOXB7 in embryonic and neoplastic cells. In a 1.9-kb 5' promoter region, we identified and functionally tested, at least in vitro, different regulatory sequences showing a direct binding by the NF-Y, YY1, Sp1/Sp3 and upstream stimulatory factor 1 (USF-1) transcription factors. Cell transfection and site-specific mutagenesis demonstrated Sp1/Sp3, NF-Y, YY1 and USF-1 binding to be functional and fundamental in driving HOXB7 expression. Disruption of the corresponding sites reduces gene expression of 65%, 78% and 55%, respectively. Because HOXB7 seems to play an important role in tumor proliferation and progression, the analysis of its regulatory sequences might represent an important step for gene targeting according to a new therapeutic strategy.
Meccia
Ettore
E
Department of Hematology and Oncology, Istituto Superiore di Sanità, Viale Regina Elena, 299- 00161, Rome, Italy.
Bottero
Lisabianca
L
Felicetti
Federica
F
Peschle
Cesare
C
Colombo
Mario P
MP
Carè
Alessandra
A
D001483:Base Sequence; D001665:Binding Sites; D023081:CCAAT-Binding Factor / Q000502:physiology; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000502:physiology; D050981:Erythroid-Specific DNA-Binding Factors; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D009154:Mutation; D011401:Promoter Regions, Genetic; D016329:Sp1 Transcription Factor / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology*; D024363:Transcription Initiation Site; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D051720:Upstream Stimulatory Factors; D050986:YY1 Transcription Factor
D023081:CCAAT-Binding Factor; D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; C490538:HOXB7 protein, human; D018398:Homeodomain Proteins; D016329:Sp1 Transcription Factor; D014157:Transcription Factors; C497181:USF1 protein, human; D051720:Upstream Stimulatory Factors; D050986:YY1 Transcription Factor; C494698:YY1 protein, human