Gfi‐1 is the transcriptional repressor of SOCS1in acute myeloid leukemia cells

SOCS1 inactivation may be caused by Gfi‐1 expression in AML cells; inhibition of H3K9 methyltransferase can rescue SOCS1 expression. Silencing of SOCS1, a TSG, has been detected in various malignancies, including AML. However, the underlying mechanism of SOCS1inactivation remains elusive. In this study, we explored the role of histone methylation in SOCS1expression in AML cells. By ChIP assay, we demonstrated that G9a and SUV39H1, two enzymes catalyzing H3K9 methylation, were physically associated with the SOCS1promoter, and treatment with chaetocin, a histone methyltransferase inhibitor, suppressed H3K9 methylation on the SOCS1promoter and enhanced SOCS1expression. Furthermore, knockdown of G9aand SUV39H1by siRNA could also induce SOCS1expression. On the other hand, SOCS1 knockdown by shRNA eliminated chaetocin‐induced cell apoptosis. To investigate further whether any transcription factor was involved in H3K9 methylation‐related SOCS1repression, we scanned the sequences of the SOCS1gene promoter and found two binding sites for Gfi‐1, a transcription repressor. By DNA pull‐down and ChIP assays, we showed that Gfi‐1 directly bound the SOCS1promoter, and ectopic Gfi‐1 expression suppressed STAT5‐induced SOCS1promoter activation. In contrast, Gfi‐1knockdown by shRNA enhanced SOCS1 expression and inhibited STAT5 expression. Moreover, the knockdown of G9acompletely rescued the repressive effect of Gfi‐1 on STAT5A‐induced SOCS1promoter activation. Collectively, our study indicates that the expression of Gfi‐1 contributes to SOCS1silencing in AML cells through epigenetic modification, and suppression of histone methyltransferase can provide new insight in AML therapy.