Aberrant epigenetic regulation has recently been implicated in the 
downregulation of tumour suppressor microRNAs (miRNAs). Histone modification and 
DNA methylation can have different roles in gene silencing in cancer. To 
investigate whether histone modifications would contribute to the dysregulation 
of miRNAs in acute lymphoblastic leukaemia (ALL), the effect of a histone 
deacetylase inhibitor, trichostatin A (TSA), on miRNA expression profile was 
analysed by microarray assay in a precursor B-cell ALL cell line NALM-6. A total 
of 10 miRNAs were downregulated and 31 were upregulated significantly following 
TSA treatment. Among TSA-upregulated miRNAs, MIR22 is an extronic miRNA and 
resides in the second exon of the non-coding transcript MGC14376. Upregulation 
of MIR22 transcription was found in both NALM-6 cells and primary human ALL 
malignant cells treated with TSA. Whereas a CpG island was identified within the 
promoter element of MIR22, no promoter DNA methylation was detected in these 
cells. In contrast, accumulation of the repressive histone marker H3K27 
trimethylation (H3K27triM) was identified around the transcriptional start point 
of the gene, which was reduced by TSA treatment. Thus, accumulation of H3K27triM 
independent of promoter DNA methylation may be a novel epigenetic mechanism for 
MIR22 silencing in ALL.