Proliferation-associated SNF2-like gene (PASG): A SNF2 family member altered in leukemia

To identify genes involved in cell growth and/or apoptosis in leukemia, dif ferential display was used to identify mRNAs that showed altered expression levels after cytokine withdrawal from the cytokine-dependent MO7e cell lin e. Sequence analysis of one transcript that showed a profound decrease in e xpression after cytokine withdrawal revealed it to be a member of the SNF2 family of chromatin remodeling ATPases. This cDNA had a 2514-nucleotide (83 8-amino acid) open reading: frame and encoded an additional WO amino acids at the NH, terminus compared with the murine homologue, Ish, and the human counterpart, Hells, This gene locus has been designated SMARCA6 (SWI/SNF2-r elated, matrix-associated, actin-dependent regulator of chromatin, subfamil y A, member 6), The highest levels of mRNA expression in humans are observe d in proliferative tissues such as the thymus, testis, and bone marrow. Whe reas cytokine withdrawal in MO7e cells leads to apoptosis and decreased mRN A expression, growth arrest without the induction of apoptosis of MO7e cell s also leads to down-regulation of mRNA expression, suggesting an associati on with cell proliferation and not suppression of apoptosis, Nuclear locali zation of this SNF2-like putative helicase is dependent on a nuclear locali zation sequence located in the NH2-terminal region. Based on sequence homol ogy to other SNF2-like helicases, the pattern of tissue expression, and the association of expression with cell proliferation, we refer to the protein product as proliferation-associated SNF2-like gene product [PASG (D, W, Le e et al., Blood, 94: 594a, 1999)], Examination of acute myelogenous leukemi a and acute lymphoblastic leukemia samples revealed a high frequency of a P ASG transcript containing an in-frame 75-nucleotide deletion, which codes f or a conserved motif known to be critical for the transactivation activity of a related yeast SWI/SNF polypeptide. These results extend our knowledge of this SNF2-like family member and suggest a role for PASG in leukemogenes is.