Viral oncogene manipulates YY1 to alter host 3D genome organization and promote B cell proliferation
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1163878 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR30761450_1.fastq.gz | Fastqsanger.gz | |||
| SRR30761450_2.fastq.gz | Fastqsanger.gz | |||
| SRR30761451_1.fastq.gz | Fastqsanger.gz | |||
| SRR30761451_2.fastq.gz | Fastqsanger.gz | |||
| SRR30761452_1.fastq.gz | Fastqsanger.gz |
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Project description:YY1 plays essential roles in regulating enhancer-promoter interactions. Here we report that Epstein-Barr virus (EBV) nuclear antigen leader protein (EBNALP), essential for EBV immortalization of naïve B lymphocytes(NBLs), manipulates YY1 to alter enhancer-promoter interactions during transformation. EBNALP colocalized with TOP2B and was tethered to DNA through DPF2 in lymphoblastoid cell lines(LCLs). EBNALP inactivation led to reduced looping at enhancers including CCND2 identified by H3K27ac HiChIP, with reduced TOP2B, DPF2, and YY1 DNA binding. EBNALP interacted with YY1 in LCLs by immune precipitation and colocalized by immunofluorescence. DPF2 CRISPR knock out reduced EBNALP and YY1 DNA binding. CRISPRi repression of CCND2 enhancers reduced CCND2 TSS H3K27ac and CCND2 expression. EBNALP also repressed enhancer looping at enhancers including CASP1. EBNALP inactivation led to increased enhancer looping with increased TOP2B, DPF2, and YY1 binding these enhancer sites.DNA accessibility increased at these sites following EBNALP inactivation by ATAC-seq. H3K9me3 was enriched at EBNALP repressed enhancer sites in LCLs.These data identified novel mechanisms through which EBVmanipulates YY1’s function to rewire host DNA elements and reorganize the host genome to facilitate EBV mediated growth transformation.
2024-12-03 | GSE277748 | GEO
Project description:The protein Yin-Yang 1 (YY1) is a ubiquitous multifunctional transcription factor. Interestingly, there are several cellular functions controlled by YY1 that could play a role in Leishmania pathogenesis. Leishmaniasis is a human disease caused by protozoan parasites of the genus Leishmania. This study examined the potential role of macrophage YY1 in promoting Leishmania intracellular survival. Knockdown of YY1 resulted in attenuated survival of Leishmania in infected macrophages, suggesting a role of YY1 in Leishmania persistence. Biochemical fractionation studies revealed Leishmania infection caused redistribution of YY1 to the cytoplasm from the nucleus where it is primarily located. Inhibition of nuclear transport by leptomycin B attenuates infection-mediated YY1 redistribution and reduces Leishmania survival. This suggests that Leishmania induces the translocation of YY1 from the nucleus to the cytoplasm of infected cells, where it may regulate host molecules to favour parasite survival. A label-free quantitative whole proteome approach showed that the expression of a large number of macrophage proteins was dependent on the YY1 level. Interestingly, several of these proteins were modulated in Leishmania-infected cells, revealing YY1-dependent host response and suggesting their potential role in Leishmania pathogenesis. Together, these findings identify YY1 as a novel and essential virulence factor by proxy that promotes Leishmania survival.
2025-03-14 | PXD059968 | Pride
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:Nucleosome positioning can alter the accessibility of DNA-binding proteins to their cognate DNA elements, and thus its precise control is essential for cell identity and function. Mammalian preimplantation embryos undergo temporal changes in gene expression and cell potency, suggesting the involvement of dynamic epigenetic control during this developmental phase. However, the dynamics of nucleosome organization during early development are poorly understood. In this study, using a low-input MNase-seq method, we show that nucleosome positioning is globally obscure in zygotes but becomes well defined during subsequent development. Downregulation of the chromatin assembly in embryonic stem cells can partially reverse nucleosome organization into a zygote-like pattern, suggesting that the chromatin assembly pathway might be linked to fuzzy nucleosomes in zygotes. We also reveal that YY1, a zinc finger containing transcription factor expressed upon zygotic genome activation, regulates the de novo formation of well-positioned nucleosome arrays at the regulatory elements, through identifying YY1-binding sites in 8-cell embryos. The YY1-binding regions acquire H3K27ac enrichment around the 8-cell and morula stages and YY1 depletion impairs the morula-to-blastocyst transition. Thus, our study delineates the remodeling of nucleosome organization and its underlying mechanism during early mouse development.
2023-07-16 | GSE220074 | GEO
Project description:YY1 plays multifaceted roles in various cell types. We recently reported that YY1 regulates nucleosome organization in early mouse embryos (Sakamoto et al. Genes Dev 2023). However, despite the impaired nucleosome organization in the absence of YY1, the transcriptome was minimally affected in eight-cell embryos. We then hypothesized that YY1 might prepare a chromatin environment to regulate gene expression at later stages. To test this possibility, we performed a transcriptome analysis at the morula stage. We found that a substantial number of genes are aberrantly expressed in the absence of YY1. Furthermore, our analysis revealed that YY1 is required for the transcription of retrotransposons in early embryos.
2023-12-26 | GSE252053 | GEO
Project description:The Epstein-Barr virus (EBV) nuclear antigen leader protein (EBNALP) is essential for the immortalization of naive B lymphocytes (NBLs). However, the mechanisms remain elusive. To understand EBNALP's role in B-cell transformation, we compare NBLs infected with wild-type EBV and an EBNALP-null mutant EBV using multi-omics techniques. EBNALP inactivation alters enhancer-promoter interactions, resulting in decreased CCND2 and increased CASP1 and BCL2L11 expression. Mechanistically, EBNALP interacts with and colocalizes with the looping factor YY1. Depletion of EBNALP reduces YY1 DNA-binding and enhancer-promoter interactions, similar to effects observed with YY1 depletion. Furthermore, EBNALP colocalizes with DPF2, a protein that binds to H3K14ac and H4K16ac. CRISPR depletion of DPF2 reduces both EBNALP and YY1 DNA binding, suggesting that the DPF2/EBNALP complex may tether YY1 to DNA to increase enhancer-promoter interactions. EBNALP inactivation also increases enhancer-promoter interactions at the CASP1 and BCL2L11 loci, along with elevated DPF2 and YY1 binding and DNA accessibility. Our data suggest that EBNALP regulates YY1 to rewire the host genome, which might facilitate naive B-cell transformation.
| S-EPMC11811279 | biostudies-literature
Project description:These data include the genome wide location analyses of Yy1 by bioChIPs of Fbio-Yy1. Streptavidin precipitation of formaldehyde cross-linked chromatin prepared from Fbio-Yy1 and control expressing mouse ES cells
2012-01-04 | E-GEOD-31785 | biostudies-arrayexpress
Project description:We mesured YY1 binding in isolated mouse crypt epihtelium using ChIP-seq Jejunal crypt epithelia were isolated and processed for ChIP using YY1 antibody Santa Cruz, SC-1703, lot E0511
2014-04-29 | E-GEOD-53502 | biostudies-arrayexpress
Project description:Higher order chromatin structure is important for regulation of genes by distal regulatory sequences. Structural variants that alter 3D genome organization can lead to enhancer-promoter rewiring and human disease, particularly in the context of cancer. However, only a small minority of structural variants are associated with altered gene expression and it remains unclear why certain structural variants lead to changes in distal gene expression and others do not. To address these questions, we used a combination of genomic profiling and genome engineering to identify sites of recurrent changes in 3D genome structure in cancer and determine the effects of specific rearrangements on oncogene activation. By analyzing Hi-C data from 92 cancer cell lines and patient samples, we identified loci affected by recurrent alterations to 3D genome structure, including oncogenes such as MYC, TERT, and CCND1. Using CRISPR/Cas9 genome engineering to generate de novo structural variants, we show that oncogene activity can be predicted using “Activity-by-Contact” models that consider partner region chromatin contacts and enhancer activity. However, Activity-by-Contact models are only predictive of specific subsets of genes in the genome, suggesting that different classes of genes engage in distinct modes of regulation by distal regulatory elements. These results indicate that structural variants that alter 3D genome organization are widespread in cancer genomes and begin to illustrate predictive rules for the consequences of structural variants on oncogene activation.
2022-10-04 | GSE147123 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE31784: Expression changes in Yy1 knock down mouse embryonic stem cells GSE31785: Yy1 occupancy of mouse ES cell genome Refer to individual Series
2012-01-04 | E-GEOD-31786 | biostudies-arrayexpress