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YY1 is involved in homologous recombination inhibition at guanine quadruplex sites in human cells

ABSTRACT: YY1 is involved in homologous recombination inhibition at guanine quadruplex sites in human cells

PROVIDER: PRJNA1072123 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR27840537_1.fastq.gz	Fastqsanger.gz
	SRR27840537_2.fastq.gz	Fastqsanger.gz
	SRR27840538_1.fastq.gz	Fastqsanger.gz
	SRR27840538_2.fastq.gz	Fastqsanger.gz
	SRR27840539_1.fastq.gz	Fastqsanger.gz

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Similar Datasets

YY1 is involved in homologous recombination inhibition at guanine quadruplex sites in human cells

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

Yin Yang 1 and guanine quadruplexes protect dopaminergic neurons from cellular stress via transmissive dormancy [YY1 CUT&RUN]

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

YY1 Controls Em-3â??RR DNA Loop Formation and Immunoglobulin Heavy Chain Class Switch Recombination.

Project description:Activation of splenic B cells induces formation of a 220kb DNA loop between Em and 3â??RR enhancers in the immunoglobulin heavy chain locus (IgH). This DNA loop has been proposed to be necessary for the crucial immune diversification mechanism of IgH class switch recombination, but the factors that control its formation are unknown. We show that conditional deletion of transcription factor YY1 in primary splenic B cells results in a dramatic drop in formation of this DNA loop, as well as immunoglobulin class switch recombination. Reconstitution of YY1-deleted splenic B cells with various YY1 mutants showed that the C-terminal half of YY1 lacking the transactivation domain restored both Em-3â??RR DNA loop formation as well as class switch recombination. RNA transcript analyses of YY1 conditional deleted splenic B cells suggest that YY1 does not regulate genes needed for DNA looping or CSR. Our results argue for a direct physical mechanism of YY1 mediating long-distance DNA loops and provide strong evidence of the importance of this DNA loop for class switching. Our results provide foundational mechanistic insight into a crucial immune function. Follicular B cells were isolated from the spleens of three C57Bl/6 yy1 fl/fl mice. For each spleen, half the cells received mock treatment and half received TATCRE. The 6 samples were then grown in RPMI medium along with LPS, Il4, OPI, and 20% FBS for 72 hours. The 6 groups of cells were lysed and RNA was isolated for library preparation. Expression differences between Mock and TATCRE treated cells were determined to understand the role of yy1 in B cell class switching.

2016-08-06 | E-GEOD-85259 | biostudies-arrayexpress

YY1 Controls Em-3’RR DNA Loop Formation and Immunoglobulin Heavy Chain Class Switch Recombination.

Project description:Activation of splenic B cells induces formation of a 220kb DNA loop between Em and 3’RR enhancers in the immunoglobulin heavy chain locus (IgH). This DNA loop has been proposed to be necessary for the crucial immune diversification mechanism of IgH class switch recombination, but the factors that control its formation are unknown. We show that conditional deletion of transcription factor YY1 in primary splenic B cells results in a dramatic drop in formation of this DNA loop, as well as immunoglobulin class switch recombination. Reconstitution of YY1-deleted splenic B cells with various YY1 mutants showed that the C-terminal half of YY1 lacking the transactivation domain restored both Em-3’RR DNA loop formation as well as class switch recombination. RNA transcript analyses of YY1 conditional deleted splenic B cells suggest that YY1 does not regulate genes needed for DNA looping or CSR. Our results argue for a direct physical mechanism of YY1 mediating long-distance DNA loops and provide strong evidence of the importance of this DNA loop for class switching. Our results provide foundational mechanistic insight into a crucial immune function.

2016-08-06 | GSE85259 | GEO

Yin Yang 1 and guanine quadruplexes protect dopaminergic neurons from cellular stress via transmissive dormancy [BG4 CUT&RUN]

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

YY1 Interacts with G quadruplex DNA to Regulate Gene Expression

Project description:YY1 Interacts with G quadruplex DNA to Regulate Gene Expression

| PRJNA595867 | ENA

The Efficacy and Safety of Fluzoparib Plus Irinotecan as Second-line Treatment in Patients With Homologous Recombination Deficiency (HRD) Metastatic Colorectal Cancer.

Project description:Preclinical data support the investigation of PARP inhibitors in other neoplasms exhibiting homologous recombination deficiency (HRD) as monotherapy as well as in combination with chemotherapy. However，in colorectal cancer (CRC), the role of HRD alterations is mostly unknown. This study aims to explore the the Efficacy and Safety of Fluzoparib combined with Irinotecan in the Second-line treatment of HRD alterations metastatic colorectal cancer.

| 8652 | ecrin-mdr-crc

Phase Separation Modulates DNA Guanine Quadruplex Formation in vitro and in cells

Project description:Phase Separation Modulates DNA Guanine Quadruplex Formation in vitro and in cells

| PRJNA937465 | ENA

Yin Yang 1 and guanine quadruplexes protect dopaminergic neurons from cellular stress via transmissive dormancy [TG timeline RNA-seq]

2024-10-28 | GSE254139 | GEO

YY1 Interacts with G quadruplex DNA to Regulate Gene Expression

Project description:We systematically analyzed the alterations in mRNA transcriptome evoked by knockdown of YY1 with or without pyridostatin (PDS) treatment. Statistical analysis showed a strong correlation between PDS-regulated and YY1-regulated genes (Pearson r > 0.67), underscoring the role of YY1-G4 structure interaction in YY1-mediated gene regulation. Moreover, the RNA-Seq results revealed that YY1 can positively or negatively regulate the expression of genes through its interaction with G4 structures.

2020-08-27 | GSE142075 | GEO

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