Figure 2

Nucleotide sequence of miR-125a/SPACA6 promoter. The sequence encompasses the 869 bp genomic segment located 3006 nucleotides upstream of pre-miR-99b that showed transcription promoter activity in the luciferase assay. INR, initiator element; DPE, downstream promoter element; uppercase, exonic sequence; bold, coding sequence; underlined, proximal enhancer containing putative binding sites for Sp1, AP-2, T-Ag, SIF, GCF, and ATF (PROSCAN 1.7); dashed underlined sequence, NF-kB binding region; TA, point mutations yielding 869mut construct. The nucleotide sequence between <and> shows an high degree of identity (82%) with the corresponding mouse genomic sequence. Nucleotides 371–381 contain methylation sites affecting miR-125a expression in acute myeloid leukemic cells, as shown by the de-methylating agent decitabine, whose cell treatment increased miR-125a expression by more than 10-fold⁶⁵.