Project description:Diverse subpopulations of astrocytes tile different brain regions to accommodate local requirements of neurons and associated neuronal circuits. Nevertheless, molecular mechanisms governing astrocyte diversity remain mostly unknown. We explored the role of a zinc finger transcription factor Yin Yang 1 (YY1) that is expressed in astrocytes. We found that specific deletion of YY1 from astrocytes causes severe motor deficits in mice, induces Bergmann gliosis, and results in simultaneous loss of GFAP expression in velate and fibrous cerebellar astrocytes. Single cell RNA-seq analysis showed that YY1 exerts specific effects on gene expression in subpopulations of cerebellar astrocytes. We found that although YY1 is dispensable for the initial stages of astrocyte development, it regulates subtype-specific gene expression during astrocyte maturation. Moreover, YY1 is continuously needed to maintain astrocyte identity in the adult cerebellum. Our findings suggest that YY1 plays critical roles regulating cerebellar astrocyte maturation during development and maintaining a mature phenotype of astrocytes in the adult cerebellum.
Project description:Investigate genes expression profiles of postmenopausal osteoporosis with kidney Yin deficiency in peripheral blood By TCM syndrome, 10 patients with postmenopausal osteoporosis were divided into three groups: kidney Yin deficiency (n=4), kidney Yang deficiency (n=3), non-kidney deficiency (n=3), another 3 healthy postmenopausal women also were selected as control group. Whole human genome oligo microarray were applied to explore gene expression difference of the groups. Kidney Yin deficiency group was compared with other three groups respectively.
Project description:Protein post-translational modification (PTM) increases the functional diversity of the proteome and regulates numerous biological processes in eukaryotes. Two types of PTMs, O-linked-acetyl glucosamine modification (O-GlcNAc) and phosphorylation have been identified on the same amino acid, are considered as Yin-Yang modification for their antagonistic function recently. Vernalization, a prolonged cold exposure promoted flowering, is important for grain yield in temperate cereals, such as winter wheat. O-GlcNAcylation on TaGRP2 and phosphorylation on VER2 are involved in regulation of vernalization response (VRN) genes. However, less is known about how plant senses vernalization with general Yin-Yang modifications. Here we report that altering O-GlcNAc signaling by chemical inhibitors could change the vernalization response and affect flowering transition. Furthermore, we enriched O-GlcNAcylated and phosphorylated peptides from winter wheat plumules at different processing time points during vernalization by Lectin weak affinity chromatography (LWAC) and iTRAQ-TiO2, respectively. In total, about 200 O-GlcNAcylated proteins and 124 differential expressed phosphorylated proteins were identified by Mass Spectrum (MS). Based on GO enrichment, the identified O-GlcNAcylated proteins are mainly involved in response to abiotic stimulus and hormone, metabolic processing and gene expression. While dynamic phosphorylated proteins during vernalization participate in translation, transcription and metabolic processing. Of note, 31 proteins with both phosphorylation and O-GlcNAcylation modification were identified. Among them, TaGRP2 was further confirmed to participate in regulation of vernalization promoted flowering. The global modification profiles and genetic data at specific regulator suggested that the dynamic network of O-GlcNAcylation and phosphorylation on the key nodes regulate vernalization response and mediate flowering in wheat.
Project description:Yin Yang 1 (YY1) and Structural Maintenance of Chromosomes 3 (SMC3) are two critical chromatin structural factors that mediate long-distance enhancer-promoter interactions and promote developmentally regulated changes in chromatin architecture in hematopoietic stem/progenitor cells (HSPCs). While YY1 plays critical functions in promoting hematopoietic stem cell (HSC) self-renewal and maintaining HSC quiescence, SMC3 is required for proper myeloid lineage differentiation. However, many questions remain unanswered regarding how YY1 and SMC3 interact with each other and impact hematopoiesis. We found that YY1 physically interacts with SMC3 and co-occupies with SMC3 at a large cohort of promoters genome-wide, and YY1 deficiency deregulates the genetic network governing cell metabolism. YY1 occupies the Smc3 promoter and represses SMC3 expression in HSPCs. YY1 regulates HSC metabolic pathways and maintains proper intracellular reactive oxygen species levels in HSCs, and this regulation is independent of YY1- SMC3 axis. Our results establish a distinct YY1-SMC3 axis and its impact on HSC quiescence and metabolism.
Project description:Protein post-translational modification (PTM) increases the functional diversity of the proteome and regulates numerous biological processes in eukaryotes. Two types of PTMs, O-linked-acetyl glucosamine modification (O-GlcNAc) and phosphorylation have been identified on the same amino acid, are considered as Yin-Yang modification for their antagonistic function recently. Vernalization, a prolonged cold exposure promoted flowering, is important for grain yield in temperate cereals, such as winter wheat. O-GlcNAcylation on TaGRP2 and phosphorylation on VER2 are involved in regulation of vernalization response (VRN) genes. However, less is known about how plant senses vernalization with general Yin-Yang modifications. Here we report that altering O-GlcNAc signaling by chemical inhibitors could change the vernalization response and affect flowering transition. Furthermore, we enriched O-GlcNAcylated and phosphorylated peptides from winter wheat plumules at different processing time points during vernalization by Lectin weak affinity chromatography (LWAC) and iTRAQ-TiO2, respectively. In total, about 200 O-GlcNAcylated proteins and 124 differential expressed phosphorylated proteins were identified by Mass Spectrum (MS). Based on GO enrichment, the identified O-GlcNAcylated proteins are mainly involved in response to abiotic stimulus and hormone, metabolic processing and gene expression. While dynamic phosphorylated proteins during vernalization participate in translation, transcription and metabolic processing. Of note, 31 proteins with both phosphorylation and O-GlcNAcylation modification were identified. Among them, TaGRP2 was further confirmed to participate in regulation of vernalization promoted flowering. The global modification profiles and genetic data at specific regulator suggested that the dynamic network of O-GlcNAcylation and phosphorylation on the key nodes regulate vernalization response and mediate flowering in wheat.
Project description:Yin Yang 1 (YY1) and Structural Maintenance of Chromosomes 3 (SMC3) are two critical chromatin structural factors that mediate long-distance enhancer-promoter interactions and promote developmentally regulated changes in chromatin architecture in hematopoietic stem/progenitor cells (HSPCs). While YY1 plays critical functions in maintaining hematopoietic stem cell (HSC) quiescence, SMC3 is required for proper lineage differentiation. However, many questions remain unanswered regarding how YY1 and SMC3 interact with each other and impact hematopoiesis. We found that YY1 physically interacts with SMC3 and co-occupies with SMC3 at a large cohort of promoters genome-wide, and YY1 deficiency deregulates the genetic network governing cell metabolism. YY1 occupies the Smc3 promoter and represses SMC3 expression in HSPCs. While deletion of one Smc3 allele partially restores HSC numbers and quiescence in YY1 knockout mice, HSC self-renewal remains defective. YY1 regulates HSC metabolic pathways and maintains proper intracellular reactive oxygen species (ROS) levels in HSCs, and this regulation is independent of YY1- SMC3 axis. Our results establish a distinct YY1-SMC3 axis and its impact on HSC quiescence, self-renewal and metabolism
Project description:Mitochondrial biogenesis requires precise regulation of both mitochondrial-encoded and nuclear-encoded genes. Nuclear receptor Nur77 is known to regulate mitochondrial metabolism in macrophages and skeletal muscle cells. Here, we compared genome-wide Nur77 binding site and target gene expression in these two cell types, which revealed conserved roles for this nuclear receptor in the regulation of nuclear-encoded mitochondrial ribosomal proteins (MRP) and enrichment of motifs for the transcription factor Yin-Yang 1 (YY1). We show that Nur77 and YY1 interact, that YY1 increases Nur77 activity, and that their binding sites are co-enriched at MRP gene loci. Nur77 and YY1 co-expression synergistically increases mitochondrial abundance and activity in macrophages but not skeletal muscle. As such, we identify a macrophage-specific Nur77-YY1 interaction that enhances mitochondrial metabolism.
Project description:Mitochondrial biogenesis requires precise regulation of both mitochondrial-encoded and nuclear-encoded genes. Nuclear receptor Nur77 is known to regulate mitochondrial metabolism in macrophages and skeletal muscle cells. Here, we compared genome-wide Nur77 binding site and target gene expression in these two cell types, which revealed conserved roles for this nuclear receptor in the regulation of nuclear-encoded mitochondrial ribosomal proteins (MRP) and enrichment of motifs for the transcription factor Yin-Yang 1 (YY1). We show that Nur77 and YY1 interact, that YY1 increases Nur77 activity, and that their binding sites are co-enriched at MRP gene loci. Nur77 and YY1 co-expression synergistically increases mitochondrial abundance and activity in macrophages but not skeletal muscle. As such, we identify a macrophage-specific Nur77-YY1 interaction that enhances mitochondrial metabolism.
Project description:Yin Yang 1 (YY1) is a multifunctional transcription factor shown to be critical in a variety of biological processes. Although it has been reported to be regulated by multiple types of post-translational modifications (PTMs), whether YY1 is methylated, which enzyme methylates YY1, and hence the functional significance of YY1 methylation remain completely unknown. Here we reported the first methyltransferase, SET7/9 (KMT7), capable of methylating YY1 in vitro and in vivo at two highly conserved lysine (K) residues, K173 and K411, located in two distinct domains, one in the central glycine-rich region and the other in the very carboxyl-terminus. Functional study revealed that SET7/9-mediated YY1 methylation regulated YY1 DNA-binding activity both in vitro and at specific genomic loci in cultured cells. Consistently, SET7/9-mediated YY1 methylation was shown to involve in YY1-regulated gene transcription and cell proliferation. Our findings revealed a novel regulatory strategy, methylation by lysine methyltransferase, imposed on YY1 protein, and linked YY1 methylation with its biological functions.
Project description:Yin Yang 1 (YY1) is a multifunctional transcription factor shown to be critical in a variety of biological processes. Although it has been reported to be regulated by multiple types of post-translational modifications (PTMs), whether YY1 is methylated, which enzyme methylates YY1, and hence the functional significance of YY1 methylation remain completely unknown. Here we reported the first methyltransferase, SET7/9 (KMT7), capable of methylating YY1 in vitro and in vivo at two highly conserved lysine (K) residues, K173 and K411, located in two distinct domains, one in the central glycine-rich region and the other in the very carboxyl-terminus. Functional study revealed that SET7/9-mediated YY1 methylation regulated YY1 DNA-binding activity both in vitro and at specific genomic loci in cultured cells. Consistently, SET7/9-mediated YY1 methylation was shown to involve in YY1-regulated gene transcription and cell proliferation. Our findings revealed a novel regulatory strategy, methylation by lysine methyltransferase, imposed on YY1 protein, and linked YY1 methylation with its biological functions.