Epigenetic modifications play an important role in human cancer. One such modification, histone methylation, contributes to human cancer through deregulation of cancer-relevant genes. The yeast Dot1 and its human counterpart, hDOT1L, methylate lysine 79 located within the globular domain of histone H3. Here we report that hDOT1L interacts with AF10, an MLL (mixed lineage leukemia) fusion partner involved in acute myeloid leukemia, through the OM-LZ region of AF10 required for MLL-AF10-mediated leukemogenesis. We demonstrate that direct fusion of hDOT1L to MLL results in leukemic transformation in an hDOT1L methyltransferase activity-dependent manner. Transformation by MLL-hDOT1L and MLL-AF10 results in upregulation of a number of leukemia-relevant genes, such as Hoxa9, concomitant with hypermethylation of H3-K79. Our studies thus establish that mistargeting of hDOT1L to Hoxa9 plays an important role in MLL-AF10-mediated leukemogenesis and suggests that the enzymatic activity of hDOT1L may provide a potential target for therapeutic intervention.

China experienced severe haze pollution in January 2013. Here we have a detailed characterization of the sources and evolution mechanisms of this haze pollution with a focus on four haze episodes that occurred during 10-14 January in Beijing. The main source of data analyzed is from submicron aerosol measurements by an Aerodyne Aerosol Chemical Speciation Monitor. The average PM1 mass concentration during the four haze episodes ranged from 144 to 300 μg m À3, which was more than 10 times higher than that observed during clean periods. All submicron aerosol species showed substantial increases during haze episodes with sulfate being the largest. Secondary inorganic species played enhanced roles in the haze formation as suggested by their elevated contributions during haze episodes. Positive matrix factorization analysis resolved six organic aerosol (OA) factors including three primary OA (POA) factors from traffic, cooking, and coal combustion emissions, respectively, and three secondary OA (SOA) factors. Overall, SOA contributed 41-59% of OA with the rest being POA. Coal combustion OA (CCOA) was the largest primary source, on average accounting for 20-32% of OA, and showed the most significant enhancement during haze episodes. A regional SOA (RSOA) was resolved for the first time which showed a pronounced peak only during the record-breaking haze episode (Ep3) on 12-13 January. The regional contributions estimated based on the steep evolution of air pollutants were found to play dominant roles for the formation of Ep3, on average accounting for 66% of PM1 during the peak of Ep3 with sulfate, CCOA, and RSOA being the largest fractions (>~75%). Our results suggest that stagnant meteorological conditions, coal combustion, secondary production, and regional transport are four main factors driving the formation and evolution of haze pollution in Beijing during wintertime.