d human keratinocytes and the skin of experimental animals. PM_2.5 was applied to human HaCaT keratinocytes at 50 µg/mL for 24 h and to mouse skin at 100 µg/mL for 7 days. The results indicate that PM_2.5 induced oxidative stress by generating reactive oxygen species both in vitro and in vivo, which led to DNA damage, lipid peroxidation, and protein carbonylation. As a result, PM_2.5 induced endoplasmic reticulum stress, mitochondrial swelling, and autophagy, and caused apoptosis in HaCaT cells and mouse skin tissue. The PM_2.5-induced cell damage was attenuated by antioxidant N-acetyl cysteine, confirming that PM_2.5 cellular toxicity was due to oxidative stress. These findings contribute to understanding of the pathophysiological mechanisms triggered in the skin by PM_2.5, among which oxidative stress may play a major role.1f:T553,Stable silencing of the INK4b-ARF-INK4a tumor suppressor locus occurs in a variety of human cancers, including malignant rhabdoid tumors (MRTs). MRTs are extremely aggressive cancers caused by the loss of the hSNF5 subunit of the SWI/SNF chromatin-remodeling complex. We found previously that, in MRT cells, hSNF5 is required for p16(INK4a) induction, mitotic checkpoint activation, and cellular senescence. Here, we investigated how the balance between Polycomb group (PcG) silencing and SWI/SNF activation affects epigenetic control of the INK4b-ARF-INK4a locus in MRT cells. hSNF5 reexpression in MRT cells caused SWI/SNF recruitment and activation of p15(INK4b) and p16(INK4a), but not of p14(ARF). Gene activation by hSNF5 is strictly dependent on the SWI/SNF motor subunit BRG1. SWI/SNF mediates eviction of the PRC1 and PRC2 PcG silencers and extensive chromatin reprogramming. Concomitant with PcG complex removal, the mixed lineage leukemia 1 (MLL1) protein is recruited and active histone marks supplant repressive ones. Strikingly, loss of PcG complexes is accompanied by DNA methyltransferase DNMT3B dissociation and reduced DNA methylation. Thus, various chromatin states can be modulated by SWI/SNF action. Collectively, these findings emphasize the close interconnectivity and dynamics of diverse chromatin modifications in cancer and gene control.20:T5a3,

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