Increased MLL-ENL expression partially overcomes the barrier to target gene activation and repression in adult progenitors. (A) MLL-ENL transcript levels in Col1a1^TetO_MLL-ENL heterozygous or homozygous mice. Transcript expression was normalized to endogenous Mll1 in each sample, as in Figure 1E. (B-E) HSC, HPC, pGM, and GMP numbers in 10-week-old, homozygous Tet-OFF-MLL-ENL mice after fetal induction. Error bars indicate standard deviations. n = 5 to 8, *P < .05, **P < .01; groups were compared with the 2-tailed Student t test. (F-H) Volcano plots show genes that are significantly induced (red) or significantly repressed (green) in HPCs, pGMs, or GMPs in 10-week-old mice that are homozygous for the Col1a1^TetO_MLL-ENL allele. The MLL-ENL transcript was mapped, and expression is indicated as a blue data point. Adjusted P values were calculated as indicated in "Materials and methods." (I-J) Numbers of unique genes that were significantly induced or repressed with a fold change >2 in P0 mice with a heterozygous Col1a1^TetO_MLL-ENL allele, as compared with adult mice with a homozygous Col1a1^TetO_MLL-ENL allele. Changes in gene expression were far more extensive in neonatal HPCs than at other time points or in other cell types, despite the presence of only a single MLL-ENL transgene. For all groups, n = 4 independent biological replicates. For panels B-E, Ctl indicates control and ME indicates Tet-OFF-MLL-ENL genotypes.