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Analysis of three-dimensional enhancer network regulated by CTCF in CD4+ T cells [HiChIP]

ABSTRACT: Purpose: We aim to analyze genome-wide changes in RNA expression, histone modifications, chromatin structure, and 3D genome organization in CD4+ T cells following CTCF depletion. Conclusions: CTCF controls gene expression via 3D enhancer network in CD4+ T cells

ORGANISM(S): Mus musculus

PROVIDER: GSE243714 | GEO | 2026/01/12

REPOSITORIES: GEO

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Analysis of three-dimensional enhancer network regulated by CTCF in CD4+ T cells [RNA-seq]

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Project description:The transcription factor ZNF143 contains seven tandem zinc fingers and is involved in 3D genome construction; however, the mechanism by which ZNF143 functions in chromatin looping remains unclear. Here, we show that ZNF143 directionally recognizes diverse genomic sites and is required for chromatin looping between these sites. In addition, ZNF143 is located between CTCF and cohesin at numerous CTCF sites and ZNF143 removal narrows the space between CTCF and cohesin. Moreover, genetic deletion of ZNF143, in conjunction with acute CTCF depletion, revealed that ZNF143 and CTCF collaborate to regulate higher-order genome organization. Thus, ZNF143 is recruited by CTCF to the CTCF sites to regulate TAD formation and genome compartmentalization whereas directional recognition of DNA motifs directly by ZNF143 itself regulates promoter activity via chromatin looping.

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Three-dimensional analysis of genome organization in CTCF-WT and CTCF-KO dendritic cells (HiChIP)

Project description:Purpose: The goals of this study are to analyze global transcriptional, epigenetic and topological changes in dendritic cells under LPS treatment condition and to investigate how CTCF regulates three-dimensional chromatin interaction in inflammatory response. Conclusions: Our study provides the detailed analysis of transcriptional, epigenetic and topological genome profiles in mouse dendritic cells under LPS treatment condition. Moreover, our data show how three-dimensional enhancer networks control gene expression during DC activation.

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CUT&RUN and HiChIP of CTCF and histone modifications in Wnt ON and Wnt OFF in HEK293T cells

Project description:We aimed to compare CTCF binding patterns, chromatin states and 3D genome structure in the absence and after activation of Wnt signaling in HEK293T cells.

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Three-dimensional regulatory hubs support oncogenic programs in glioblastoma [HiChIP]

Project description:Enhancer-promoter communication in the context of the three-dimensional (3D) nucleus is critical for the regulation of transcriptional programs specific for cell identity. Here, we profile the 3D enhancer-promoter networks of primary patient-derived human glioma spheres (GSCs) in comparison with neuronal stem cells to identify candidate central nodes of GSC tumorigenic programs. We have identified highly interacting 3D enhancer-promoter “hubs” which strongly associate with robust and coordinated expression of tumor-associated genes, suggesting potentially central roles in the regulation of oncogenic programs. Integration of whole-genome sequencing (WGS) data from The Cancer Genome Atlas showed that 3D regulatory hubs are strongly enriched for recurrent point mutations in the larger cohort of glioblastoma patients. In a proof-of-concept experiment, epigenetic perturbation of a highly interacting and recurrent 3D enhancer hub in the GOLIM4 locus led to significant downregulation of multiple hub-connected genes and reduced clonogenicity along with a global shift in the transcriptional states. Finally, integration of published H3K27ac HiChIP from other cancer types enabled the identification of both “universal” and cancer type-specific 3D regulatory hubs which enrich for different oncogenic programs and potential regulators, and often associate with a worse prognosis. Overall, our study identifies complex 3D regulatory hubs in glioblastoma and provides computational and experimental support for their potential role in driving oncogenic programs and promoting tumorigenic properties.

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