Regulation of the LIFR and gp130 genes by the RUNX1 transcription factor

摘要: The RUNX1 transcription factor is an important regulator of haematopoiesis and has been found to influence gene activity at both the transcriptional chromatin levels. In leukaemia, particularly Acute Myeloid Leukaemia, frequently altered by point mutations chromosomal rearrangements, most common being t(8;21) translocation that produces a RUNX1-ETO fusion protein. While generally associated with activation, mainly acts as repressor its presence therefore expression target genes. Previous microarray analysis performed in our laboratory identified LIFR gp130 genes novel putative targets. together forms heterodimeric receptor complex mediates LIF signalling, doing so controls various cellular processes including development, differentiation inflammatory responses. However, despite their biological roles little known about regulation Bioinformatic potential binding sites promoters genes, this study examined hypothesis are leukemic cells which disrupted may contribute leukaemia. The regulated alternate promoters, called ‘general’ ‘placental’ promoter previously described. Analysis mRNA across number cell types demonstrated placental limited lines origin, while general active range types, myeloid cells. This was confirmed status two general, but not assembled into highly acetylated histones detected all examined. Reporter can be activated respectively. addition, lines. contrast, repressed Further, endogenous immunoprecipitation, suggesting targeted RUNX1. support knockdown reduced lines, decreased transcript Put together, data presented thesis demonstrates regulates LIFR/gp130 likely leukaemic altered.