HY5: A Pivotal Regulator of Light-Dependent Development in Higher Plants

ELONGATED HYPOCOTYL5 (HY5), a bZIP-type transcription factor, acts as a master regulator that regulates various physiological and biological processes in plants such as photomorphogenesis, root growth, flavonoid biosynthesis and accumulation, nutrient acquisition, and response to abiotic stresses. HY5 is evolutionally conserved in function among various plant species. HY5 acts as a master regulator of light-mediated transcriptional regulatory hub that directly or indirectly controls the transcription of approximately one-third of genes at the whole genome level. The transcription, protein abundance, and activity of HY5 are tightly modulated by a variety of factors through distinct regulatory mechanisms. This review primarily summarizes recent advances on HY5-mediated molecular and physiological processes and regulatory mechanisms on HY5 in the model plant Arabidopsis as well as in crops.

PP2A-dependent TFEB activation is blocked by PIKfyve-induced mTORC1 activity

Transcriptional factor EB (TFEB) is a master regulator of genes required for autophagy and lysosomal function. The nuclear localization of TFEB is blocked by the mechanistic target of rapamycin complex 1 (mTORC1)-dependent phosphorylation of TFEB at multiple sites including Ser-211. Here we show that inhibition of PIKfyve, which produces phosphatidylinositol 3,5-bisphosphate on endosomes and lysosomes, causes a loss of Ser-211 phosphorylation and concomitant nuclear localization of TFEB. We found that while mTORC1 activity toward S6K1, as well as other major mTORC1 substrates, is not impaired, PIKfyve inhibition specifically impedes the interaction of TFEB with mTORC1. This suggests that mTORC1 activity on TFEB is selectively inhibited due to loss of mTORC1 access to TFEB. In addition, we found that TFEB activation during inhibition of PIKfyve relies on the ability of protein phosphatase 2A (PP2A) but not calcineurin/PPP3, to dephosphorylate TFEB Ser-211. Thus, when PIKfyve is inhibited, PP2A is dominant over mTORC1 for control of TFEB phosphorylation at Ser-S211. Together these findings suggest that mTORC1 and PP2A have opposing roles on TFEB via phosphorylation and dephosphorylation of Ser-211, respectively, and further, that PIKfyve inhibits TFEB activity by facilitating mTORC1-dependent phosphorylation of TFEB.

Bacillus subtilis Histidine Kinase KinC Activates Biofilm Formation by Controlling Heterogeneity of Single-Cell Responses

In many bacterial and eukaryotic systems, multiple cell fate decisions are activated by a single master regulator. Typically, the activities of the regulators are controlled posttranslationally in response to different environmental stimuli.

Single-Cell Analysis Identify Transcription Factor BACH1 as a Master Regulator Gene in Vascular Cells During Aging

Vascular aging is a potent driver of cardiovascular and cerebrovascular diseases. Vascular aging features cellular and functional changes, while its molecular mechanisms and the cell heterogeneity are poorly understood. This study aims to 1) explore the cellular and molecular properties of aged cardiac vasculature in monkey and mouse and 2) demonstrate the role of transcription factor BACH1 in the regulation of endothelial cell (EC) senescence and its mechanisms. Here we analyzed published single-cell RNA sequencing (scRNA-seq) data from monkey coronary arteries and aortic arches and mouse hearts. We revealed that the gene expression of YAP1, insulin receptor, and VEGF receptor 2 was downregulated in both aged ECs of coronary arteries’ of monkey and aged cardiac capillary ECs of mouse, and proliferation-related cardiac capillary ECs were significantly decreased in aged mouse. Increased interaction of ECs and immunocytes was observed in aged vasculature of both monkey and mouse. Gene regulatory network analysis identified BACH1 as a master regulator of aging-related genes in both coronary and aorta ECs of monkey and cardiac ECs of mouse. The expression of BACH1 was upregulated in aged cardiac ECs and aortas of mouse. BACH1 aggravated endothelial cell senescence under oxidative stress. Mechanistically, BACH1 occupied at regions of open chromatin and bound to CDKN1A (encoding for P21) gene enhancers, activating its transcription in senescent human umbilical vein endothelial cells (HUVECs). Thus, these findings demonstrate that BACH1 plays an important role in endothelial cell senescence and vascular aging.

Expression of pluripotency-related genes in human glioblastoma

Background Cancer is a group of heterogeneous diseases characterized by several disruptions of the genetic and epigenetic components of cell biology. Some types of cancer have been shown to be constituted by a mosaic of cells with variable differentiation states, with more aggressive tumors being more undifferentiated. In most cases, undifferentiated tumor cells express associated embryonic markers such as the OCT4, NANOG, SOX2 and CARM1 genes. The ectopic or reminiscent expression of some master regulator genes of pluripotency has been indicated as the cause of the poorly differentiated state of tumors, and based on the evidence of some reports, can be used as a possible therapeutic target. Considering this information, a more detailed investigation of the expression of pluripotency-associated genes is necessary to evaluate the roles of these genes in the etiology of some tumors and their use targets of therapy. Methods The expression of four pluripotency-related genes was investigated (OCT4, NANOG, SOX2 and CARM1) in the most malignant primary human brain tumor, glioblastoma (GBM). Results and Conclusion The results demonstrated a signature of OCT4/SOX2/CARM1 genes and a significant increase of CARM1 expression in GBM cases.

Epigenetic Age Acceleration Is Not Associated with Age-Related Macular Degeneration

DNA methylation age (DNAm age) estimation is a powerful biomarker of human ageing. To date, epigenetic clocks have not been evaluated in age-related macular degeneration (AMD). Here, we perform genome-wide DNA methylation analyses in blood of AMD patients with a documented smoking history (14 AMD, 16 Normal), identifying loci of differential methylation (DML) with a relaxed p-value criterion (p ≤ 10−4). We conduct DNAm age analyses using the Horvath-multi tissue, Hannum and Skin & Blood epigenetic clocks in both blood and retinal pigment epithelium (RPE). We perform Ingenuity Pathway Analysis Causal Network Analysis (IPA CNA) on the topmost significantly differentially methylated CpG probes in blood and RPE. Results show poor performance of epigenetic clocks in RPE. Epigenetic age acceleration (EAA) was not observed in AMD. However, we observe positive EAA in blood of smokers, and in smokers with AMD. DML analysis revealed hypomethylation at cg04953735 within RPTOR (p = 6.51 × 10−5; Δβ = −11.95%). IPA CNA in the RPE also identified RPTOR as the putative master regulator, predicted to be inhibited in AMD. In conclusion, this is the first study evaluating an association of epigenetic ageing in AMD. We posit a role for RPTOR as a common master regulator of methylation changes in the RPE in AMD.