YY1 Interacts with G quadruplex DNA to Regulate Gene Expression
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ABSTRACT:
PROVIDER: PRJNA595867 | ENA |
REPOSITORIES: ENA
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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
Project description:YY1 regulates DNA-DNA interaction
| PRJNA526477 | ENA
Project description:The G-quadruplex is an alternative DNA structural motif that is considered to be functionally important in the mammalian genome. Herein, we address the hypothesis that G-quadruplex structures can exist within double-stranded genomic DNA using a G-quadruplex-specific probe. An engineered antibody is employed to enrich for DNA containing G-quadruplex structures, followed by deep sequencing to detect and map G-quadruplexes at high resolution in genomic DNA from human breast adenocarcinoma cells. Our high sensitivity structure-based pull-down strategy enables the isolation of genomic DNA fragments bearing a single as well as multiple G-quadruplex structures. Stable G-quadruplex structures are found in sub-telomeres, gene bodies and gene regulatory regions. For a sample of identified target genes, we show that G-quadruplex stabilizing ligands can modulate transcription. These results confirm the existence of G-quadruplex structures and their persistence in human genomic DNA. Four independent libraries have been enriched in DNA G-quadruplex structures using a G-quadruplex-specific probe. One genomic input library was sequenced as control. Deep-sequencing of these libraries allowed the mapping of G-quadruplexes on the genome.
2013-05-08 | E-GEOD-45241 | biostudies-arrayexpress
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:YY1 is a ubiquitously expressed, intrinsically disordered transcription factor involved in neural development. The oligomeric state of YY1 varies depending on the environment. These changes may alter its DNA binding ability and hence its transcriptional activity. In addition to its oligomeric state, the interaction of YY1 with proteins such as FOXP2 can impact its role in transcription. The aim of this work is to study the structure and dynamics of YY1 binding to DNA and to determine the influence of oligomerisation and associations with FOXP2 on its DNA binding mechanism. Size exclusion chromatography, fluorescence anisotropy and electrophoretic mobility shift assays were used to study YY1 oligomerisation and interaction with FOXP2. To better understand potential structural changes to YY1 upon DNA binding, hydrogen deuterium exchange mass spectrometry was used. The results indicate that YY1 consists of specific structured regions, while most of the sequence remains disordered. Furthermore, the oligomeric nature of the protein is dependent on ionic strength. DNA affects oligomerisation and the protein undergoes changes in structure and dynamics upon DNA binding. YY1 and FOXP2 were found to interact with each other both in isolation and in the presence of YY1-specific DNA. The heterogeneous, dynamic multimerisation of YY1 identified in this work is, therefore, likely to be important for its ability to make heterologous associations with other proteins such as FOXP2. The interactions that YY1 forms with itself, FOXP2 and DNA form part of an intricate mechanism of transcriptional regulation by YY1, which is vital for appropriate neural development.
2024-01-26 | PXD038431 | Pride
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
Project description:The G-quadruplex is an alternative DNA structural motif that is considered to be functionally important in the mammalian genome. Herein, we address the hypothesis that G-quadruplex structures can exist within double-stranded genomic DNA using a G-quadruplex-specific probe. An engineered antibody is employed to enrich for DNA containing G-quadruplex structures, followed by deep sequencing to detect and map G-quadruplexes at high resolution in genomic DNA from human breast adenocarcinoma cells. Our high sensitivity structure-based pull-down strategy enables the isolation of genomic DNA fragments bearing a single as well as multiple G-quadruplex structures. Stable G-quadruplex structures are found in sub-telomeres, gene bodies and gene regulatory regions. For a sample of identified target genes, we show that G-quadruplex stabilizing ligands can modulate transcription. These results confirm the existence of G-quadruplex structures and their persistence in human genomic DNA.
2013-05-08 | GSE45241 | GEO
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
Project description:G-quadruplex structures moulds the DNA methylome
| PRJNA421087 | ENA
Project description:In this study we discover proteins that bind to G4 quadruplex DNA structure. We use modified c-myc quadruplex as a bait, and compare it to the control bait - T15 oligo. We use spectral counts and G-test to determine significant binders. T15 and G4 datafiles are uploaded
2016-07-07 | PXD003501 | Pride