Transcriptional cross-regulation of RUNX1 by RUNX3 in human B cells.
RUNX transcription factors are important in development and in numerous types of human cancer. They act as either transcriptional activators or repressors and can be proto-oncogenes or tumour suppressors. Understanding their regulation and interaction may explain how RUNX factors contribute to such different and often opposing biological processes. We show that RUNX3 regulates RUNX1 expression, contributing to the mutually exclusive expression of RUNX3 and RUNX1 in human B lymphoid cell lines. RUNX3 repressed the RUNX1 P1 promoter by binding specifically to conserved RUNX sites near the transcription start of the promoter. siRNA inhibition of RUNX3 in lymphoblastoid cells resulted in increased RUNX1 expression, indicating that continuous expression of physiological levels of RUNX3 is required to maintain repression. Furthermore, expression of RUNX3 was required for efficient proliferation of B cells immortalized by Epstein-Barr virus. Cross-regulation between different RUNX family members is therefore a means of controlling RUNX protein expression and must now be considered in the interpretation of pathological changes due to loss of RUNX3 tumour suppressor function or following gene duplication or translocation events.
Spender
Lindsay C
LC
Department of Virology, Ludwig Institute for Cancer Research, Imperial College Faculty of Medicine, Norfork Place, St Mary's Campus, Norfolk Place, London W2 1PG, UK.
Whiteman
Hannah J
HJ
Karstegl
Claudio Elgueta
CE
Farrell
Paul J
PJ
D001402:B-Lymphocytes / Q000502:physiology* / Q000821:virology; D001483:Base Sequence; D050676:Core Binding Factor Alpha 2 Subunit; D050677:Core Binding Factor Alpha 3 Subunit; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology*; D020440:Gene Duplication; D005786:Gene Expression Regulation; D004854:Herpesvirus 4, Human; D006801:Humans; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D011994:Recombinant Proteins / Q000378:metabolism; D015183:Restriction Mapping; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology*; D014158:Transcription, Genetic; D014162:Transfection; D014178:Translocation, Genetic
D050676:Core Binding Factor Alpha 2 Subunit; D050677:Core Binding Factor Alpha 3 Subunit; D017931:DNA Primers; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; C493728:RUNX1 protein, human; D011994:Recombinant Proteins; C493729:Runx3 protein, human; D014157:Transcription Factors