Yin Yang 1 and guanine quadruplexes protect dopaminergic neurons from cellular stress via transmissive dormancy [YY1 CUT&RUN]
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ABSTRACT:
PROVIDER: PRJNA1068976 | ENA |
REPOSITORIES: ENA
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Project description:Neurons deploy diverse adaptive strategies to ensure survival and neurotransmission amid cellular stress. Yet, when these adaptive pathways are overwhelmed, functional impairment or neurodegeneration follow. Herein we report a scenario where stressed neurons actively adopt a state of transmissive dormancy, despite rapid activation of stress response pathways, as a terminal protective measure. Examination of dopaminergic neurons surviving severe cellular stress, revealed decreased spontaneous activity accompanied by dynamic control of dopamine metabolism through the Yin Yang 1 (YY1) transcriptional regulator. Under conditions of ionic imbalance or oxidative stress, YY1 promotes expression of the SLC18A2 transporter with the capacity to enhance sequestration of dopamine into transport vesicles. Subsequent DNA damage represses the rate-limiting enzyme in dopamine synthesis, tyrosine hydroxylase (TH), through YY1 mediated stabilization of an intronic guanine quadruplex. This cascade has the potential to drive circuit inactivation and safeguard neurons by minimizing the toxic accumulation of cytosolic dopamine and reducing the energetic expenditure associated with cellular depolarization. In essence, neurons appear to actively prioritize viability over functionality.
2024-10-28 | GSE254192 | GEO
Project description:Neurons deploy diverse adaptive strategies to ensure survival and neurotransmission amid cellular stress. When these adaptive pathways are overwhelmed, functional impairment or neurodegeneration follows. Here, we report a scenario where stressed neurons actively induce a state of transmissive dormancy as a protective measure. Examination of dopaminergic neurons surviving severe cellular challenges revealed decreased spontaneous activity accompanied by dynamic control of dopamine metabolism through the transcriptional regulator Yin Yang 1 (YY1). Under these conditions, YY1 increases expression of the vesicular monoamine transporter 2, promoting sequestration of dopamine into synaptic vesicles. Following oxidative stress and subsequent DNA damage, YY1 inhibits dopamine synthesis through stabilization of a guanine quadruplex in intron 10 of tyrosine hydroxylase. This cytoprotective response has the potential to drive circuit inactivation and safeguard neurons by minimizing the toxic accumulation of cytosolic dopamine and inducing a state of neuronal dormancy. In essence, neurons appear to actively prioritize viability over functionality.
2024-10-28 | GSE275940 | GEO
Project description:Neurons deploy diverse adaptive strategies to ensure survival and neurotransmission amid cellular stress. Yet, when these adaptive pathways are overwhelmed, functional impairment or neurodegeneration follow. Herein we report a scenario where stressed neurons actively adopt a state of transmissive dormancy, despite rapid activation of stress response pathways, as a terminal protective measure. Examination of dopaminergic neurons surviving severe cellular stress, revealed decreased spontaneous activity accompanied by dynamic control of dopamine metabolism through the Yin Yang 1 (YY1) transcriptional regulator. Under conditions of ionic imbalance or oxidative stress, YY1 promotes expression of the SLC18A2 transporter with the capacity to enhance sequestration of dopamine into transport vesicles. Subsequent DNA damage represses the rate-limiting enzyme in dopamine synthesis, tyrosine hydroxylase (TH), through YY1 mediated stabilization of an intronic guanine quadruplex. This cascade has the potential to drive circuit inactivation and safeguard neurons by minimizing the toxic accumulation of cytosolic dopamine and reducing the energetic expenditure associated with cellular depolarization. In essence, neurons appear to actively prioritize viability over functionality.
2024-10-28 | GSE254139 | GEO
Project description:Yin Yang 1 and guanine quadruplexes protect dopaminergic neurons from cellular stress via transmissive dormancy
| PRJNA1068969 | ENA
Project description:Yin Yang 1 and guanine quadruplexes protect dopaminergic neurons from cellular stress via transmissive dormancy [BG4 CUT&RUN]
| PRJNA1153920 | ENA
Project description:The DNA Guanine quadruplexes (G4) plays important roles in multiple cellular processes, including regulation of DNA replication, transcription and genome stability. Here, we show that Yin Yang-1 (YY1), a ubiquitously expressed and multifunctional transcription factor, can bind with G4 structures directly. Fluorescence anisotropy experiments shows that YY1 binds towards G4 structures with Kd in low nanomolar range (<100 nM) through the C terminal zinc finger domains. ChIP-seq results show that 81% of the YY1 ChIP-seq peaks contain G4 forming sequences, which is highly overlapped with the G4 ChIP-seq peaks. YY1 facilitate the DNA-DNA interaction through its binding with G4 structures in vivo and in vitro, which can be disturbed by G4 stabilizer treatment. In all, our studies identify a novel G4 structure binding protein-YY1, and reveal that G4 structure functions in DNA-DNA interaction.
2020-08-27 | GSE128106 | GEO
Project description:Yin Yang 1 and guanine quadruplexes protect dopaminergic neurons from cellular stress via transmissive dormancy [TG timeline RNA-seq]
| PRJNA1068619 | ENA
Project description:Homologous recombination (HR) is a key process for repairing DNA double strand breaks and for promoting genetic diversity, and it occurs unevenly throughout the genome. G-quadruplexes (G4s) are stable secondary structures widely present across the genome, which function in regulating gene transcription and maintaining genome stability. However, elevated G4 levels by BLM (RecQ like helicase unwinding G4) depletion can significantly drive HR at these G4 sites, which may threaten genome stability. Here, we investigated the role of Yin Yang-1 (YY1) in modulating HR at G4 sites. To elucidate G4 sites on the genome, cleavage under targets and tagmentation (CUT&Tag) of BG4, a G4 specific antibody, was conducted.
2024-05-29 | GSE254872 | GEO
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.
2022-04-01 | GSE166792 | GEO
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.
2024-03-11 | GSE261032 | GEO