<p dir="ltr">Nitrogen (N) is a macronutrient required for plant growth and is a major constituent of nucleic acids and proteins that are essential for several life processes. Plant response to N has been well understood at a molecular level but little is known about the chromatin or epigenetic level regulation of N response. Uncovering the epigenetic level regulation essential for plant N signaling and response is essential to improving our molecular understanding of N use efficiency (NUE). To fill this knowledge gap, we first performed a meta-analysis intersecting the published transcriptomic study of N-responsive genes in <i>Arabidopsis thaliana </i>with EpiNet, an extensive epigenetic regulatory network previously constructed in our lab through machine learning approaches, to identify a list of 18 potential epigenetic regulators that are predicted to control N response in plants. Next, by adopting a reverse genetics approach, we aimed to validate the <i>in-silico</i> prediction of these essential epigenetic regulators. To do this, we grew T-DNA insertional mutants for the genes encoding these epigenetic regulators, along with wild-type controls, under high and low N conditions, and compared them in various physiological traits. Our results indicate that 8 out of 10 confirmed knock-down mutants do show altered N-responsive phenotypes in comparison to the wild type. One of the mutants, <i>ashr2-1, </i>which is mutated in a gene encoding a putative SET-domain containing group protein (SDG) of putative histone methyltransferase, displayed reduced growth of primary root compared to WT in response to N. We performed RNA-sequencing to identify the differentially expressed genes that are induced or repressed by ASHR2 in N treatments to gain further insight into the molecular underpinnings of the ASHR2-mdediated N response in roots<i>.</i> In summary, our study has revealed knowledge on important epigenetic regulators in plant N responses, which has the potential to be extended to crop species as novel targets for enhancing NUE.</p>

No / The epidermal differentiation program is regulated at several levels including signaling pathways, lineage-specific transcription factors, and epigenetic regulators that establish well-coordinated process of terminal differentiation resulting in formation of the epidermal barrier. The epigenetic regulatory machinery operates at several levels including modulation of covalent DNA/histone modifications, as well as through higher-order chromatin remodeling to establish long-range topological interactions between the genes and their enhancer elements. Epigenetic regulators exhibit both activating and repressive effects on chromatin in keratinocytes (KCs): whereas some of them promote terminal differentiation, the others stimulate proliferation of progenitor cells, as well as inhibit premature activation of terminal differentiation-associated genes. Transcription factor-regulated and epigenetic mechanisms are highly connected, and the p63 transcription factor has an important role in the higher-order chromatin remodeling of the KC-specific gene loci via direct control of the genome organizer Satb1 and ATP-dependent chromatin remodeler Brg1. However, additional efforts are required to fully understand the complexity of interactions between distinct transcription factors and epigenetic regulators in the control of KC differentiation. Further understanding of these interactions and their alterations in different pathological skin conditions will help to progress toward the development of novel approaches for the treatment of skin disorders by targeting epigenetic regulators and modulating chromatin organization in KCs. / National Alopecia Areata Foundation; (R13AR067088-01) from the National Institute of Arthritis and Musculoskeletal and Skin Diseases; and the National Center for Advancing Translational Sciences