Climate forcing effects of tropospheric aerosols are determined by their relative abilities to absorb and scatter light and also their effects on cloud properties and lifetime, which may lead to net warming or cooling of the atmosphere. Many details of the formation and lifecycle of organic content that contributes to aerosol light absorption, termed brown carbon (BrC), remain uncertain after extensive study. The reactive species that form BrC make up only a small fraction of total aerosol organic content, and the overwhelming remainder of organic content could greatly influence the rate of BrC formation. One significant route to BrC formation is the reaction of water-soluble carbonyl species to form larger conjugated and/or aromatic compounds, such as the reaction of di-aldehydes (e.g., glyoxal) with reduced nitrogen species (ammonia or amines) to form imidazole derivatives. In this study, we work to further address the complexity of atmospheric aerosols by adding a matrix of organic content to the glyoxal–ammonium system. We find that the addition of a broad range of organic species (alcohols, ketones, organic acids, etc.) to BrC-forming reaction mixtures can both increase and decrease the rate of BrC formation. The rate of BrC formation is shown to vary by more than an order of magnitude depending on the composition of the organic matrix present. UV–vis kinetic measurements and HPLC-ToF-MS product analysis of aqueous solutions with qualities similar to atmospheric aerosols reveal the specific steps in BrC formation affected by the presence of organic content. Our method of systematically adding complexity also proves a useful tool for mechanistic evaluation, and we provide evidence that the proposed cis-di-imine mechanism for the reaction of ammonia and glyoxal is unlikely, with amine species reacting instead.

Supplementary Figure from <i>BCOR</i> and <i>BCORL1</i> Mutations Drive Epigenetic Reprogramming and Oncogenic Signaling by Unlinking PRC1.1 from Target Genes

<div>Abstract<p>Polycomb repressive epigenetic complexes are recurrently dysregulated in cancer. Unlike polycomb repressive complex 2 (PRC2), the role of PRC1 in oncogenesis and therapy resistance is not well-defined. Here, we demonstrate that highly recurrent mutations of the PRC1 subunits <i>BCOR</i> and <i>BCORL1</i> in leukemia disrupt assembly of a noncanonical PRC1.1 complex, thereby selectively unlinking the RING-PCGF enzymatic core from the chromatin-targeting auxiliary subcomplex. As a result, <i>BCOR</i>-mutated PRC1.1 is localized to chromatin but lacks repressive activity, leading to epigenetic reprogramming and transcriptional activation at target loci. We define a set of functional targets that drive aberrant oncogenic signaling programs in PRC1.1-mutated cells and primary patient samples. Activation of these PRC1.1 targets in <i>BCOR</i>-mutated cells confers acquired resistance to treatment while sensitizing to targeted kinase inhibition. Our study thus reveals a novel epigenetic mechanism that explains PRC1.1 tumor-suppressive activity and identifies a therapeutic strategy in PRC1.1-mutated cancer.</p>Significance:<p>We demonstrate that <i>BCOR</i> and <i>BCORL1</i> mutations in leukemia unlink PRC1.1 repressive function from target genes, resulting in epigenetic reprogramming and activation of aberrant cell signaling programs that mediate treatment resistance. Our study provides mechanistic insights into the pathogenesis of PRC1.1-mutated leukemia that inform novel therapeutic approaches.</p><p><i>This article is highlighted in the In This Issue feature, p. 85</i></p></div>

Supplementary Data from <i>BCOR</i> and <i>BCORL1</i> Mutations Drive Epigenetic Reprogramming and Oncogenic Signaling by Unlinking PRC1.1 from Target Genes

<div>Abstract<p>Polycomb repressive epigenetic complexes are recurrently dysregulated in cancer. Unlike polycomb repressive complex 2 (PRC2), the role of PRC1 in oncogenesis and therapy resistance is not well-defined. Here, we demonstrate that highly recurrent mutations of the PRC1 subunits <i>BCOR</i> and <i>BCORL1</i> in leukemia disrupt assembly of a noncanonical PRC1.1 complex, thereby selectively unlinking the RING-PCGF enzymatic core from the chromatin-targeting auxiliary subcomplex. As a result, <i>BCOR</i>-mutated PRC1.1 is localized to chromatin but lacks repressive activity, leading to epigenetic reprogramming and transcriptional activation at target loci. We define a set of functional targets that drive aberrant oncogenic signaling programs in PRC1.1-mutated cells and primary patient samples. Activation of these PRC1.1 targets in <i>BCOR</i>-mutated cells confers acquired resistance to treatment while sensitizing to targeted kinase inhibition. Our study thus reveals a novel epigenetic mechanism that explains PRC1.1 tumor-suppressive activity and identifies a therapeutic strategy in PRC1.1-mutated cancer.</p>Significance:<p>We demonstrate that <i>BCOR</i> and <i>BCORL1</i> mutations in leukemia unlink PRC1.1 repressive function from target genes, resulting in epigenetic reprogramming and activation of aberrant cell signaling programs that mediate treatment resistance. Our study provides mechanistic insights into the pathogenesis of PRC1.1-mutated leukemia that inform novel therapeutic approaches.</p><p><i>This article is highlighted in the In This Issue feature, p. 85</i></p></div>