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N 6 -methyladenosine (m 6 A) is a commonly present modification of mammalian mRNAs and plays key roles in various cellular processes. m 6 A modifiers catalyze this reversible modification. However, the underlying mechanisms by which these m 6 A modifiers are regulated remain elusive. Here we show that expression of m 6 A demethylase ALKBH5 is regulated by chromatin state alteration during leukemogenesis of human acute myeloid leukemia (AML), and ALKBH5 is required for maintaining leukemia stem cell (LSC) function but is dispensable for normal hematopoiesis. Mechanistically, KDM4C regulates ALKBH5 expression via increasing chromatin accessibility of ALKBH5 locus, by reducing H3K9me3 levels and promoting recruitment of MYB and Pol II. Moreover, ALKBH5 affects mRNA stability of receptor tyrosine kinase AXL in an m 6 Adependent way. Thus, our findings link chromatin state dynamics with expression regulation of m 6 A modifiers and uncover a selective and critical role of ALKBH5 in AML that might act as a therapeutic target of specific targeting LSCs.

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The aim of this study was to determine the effects of high temperature stress on ammonium assimilation in leaves of two tall fescue cultivars (Festuca arundinacea), Jaguar 3 brand (J3) (heat-tolerant) and TF 66 (T6) (heatsensitive). High temperature stress for either 10 d or 20 d, and particularly the 20 d stress, produced dramatic changes in ammonium assimilation. After 20 d of stress treatment, the accumulations of total nitrogen, nitrate, soluble protein and total free amino acid (20 amino acids) decreased in both cultivars. Moreover, the activities of main regulatory enzymes, such as nitrate reductase, glutamine synthetase (GS), NADH-dependent glutamate synthase (GOGAT), as well as D 1 -pyrroline-5-carboxylate reductase (P5CR), also decreased in both cultivars when exposed to 20 d stress. Heat stress had little influence on ammonium accumulation in J3, but this was not the case with T6. The accumulations of nitrate, ammonium, soluble protein, and total free amino acid between the two cultivars were different. This suggests that accumulations of these nitrogen forms were associated with heat tolerance in both tall fescue cultivars. Changes of both NADH-glutamate dehydrogenase (NADH-GDH) activity and Glx (glutamine and glutamic acid) concentration in both cultivars indicated that there is an alternative system for assimilation of nitrogen through glutamate dehydrogenase (GDH) in T6 during longer high temperature stress periods. Our results provide an insight to further selection and breeding of heat-tolerant tall fescue turfgrass cultivars. KeywordsAmmonium assimilation AE Festuca arundinacea AE Free amino acid AE High temperature stress AE Nitrogen Abbreviations DW Dry weight FW Fresh weight GS Glutamine synthetase J3 Jaguar 3 brand NADH-GDH NADH-dependent glutamate dehydrogenase NADH-GOGAT NADH-dependent glutamate synthase

Heat shock factors (Hsfs) are important regulators of stress-response in plants. However, our understanding of Hsf genes and their responses to temperature stresses in two Pooideae cool-season grasses, Festuca arundinacea, and Lolium perenne, is limited. Here we conducted comparative transcriptome analyses of plant leaves exposed to heat or cold stress for 10 h. Approximately, 30% and 25% of the genes expressed in the two species showed significant changes under heat and cold stress, respectively, including subsets of Hsfs and their target genes. We uncovered 74 Hsfs in F. arundinacea and 52 Hsfs in L. perenne, and categorized these genes into three subfamilies, HsfA, HsfB, and HsfC based on protein sequence homology to known Hsf members in model organisms. The Hsfs showed a strong response to heat and/or cold stress. The expression of HsfAs was elevated under heat stress, especially in class HsfA2, which exhibited the most dramatic responses. HsfBs were upregulated by the both temperature conditions, and HsfCs mainly showed an increase in expression under cold stress. The target genes of Hsfs, such as heat shock protein (HSP), ascorbate peroxidase (APX), inositol-3-phosphate synthase (IPS), and galactinol synthase (GOLS1), showed strong and unique responses to different stressors. We comprehensively detected Hsfs and their target genes in F. arundinacea and L. perenne, providing a foundation for future gene function studies and genetic engineering to improve stress tolerance in grasses and other crops.