Dataset Information

SCOPE-C Reveals the Key Role of Long-Range Loop Extrusion in Dynamic Enhancer Networks for Robust Gene Activation in Human Fetal Cortical Neurogenesis

ABSTRACT: The chromatin in the human brain cortex exhibits a higher number of enhancer-enhancer (E-E) contacts compared to macaques and mice. However, the specific organization of these E-E contacts across different cellular states, as well as the mechanisms for associating these dynamic enhancer interaction networks with particular genes, remain poorly understood. Here, we present SCOPE-C, a cost-effective technique designed for mapping DNase I Hypersensitive Sites (DHSs) and enriching their spatial interactions, with a remarkable capacity to handle samples as small as 1 to 1,000 cells. Employing SCOPE-C, we generated a comprehensive chromatin map detailing cis-regulatory elements (CREs) in the developing fetal cortex across human, macaque, and mouse species, utilizing data from Radial Glia (RG), Intermediate Progenitor Cells (IPCs), Excitatory Neurons (ENs), and Interneurons (INs) collected at similar mid-gestation stages. This map reveals dynamic enhancer interaction hubs and their target genes during cortical neurogenesis. We find that loop extrusion profoundly shapes these dynamic interaction networks, forming 'stripes' that can extend up to 10Mb in ENs and exhibit species-specific dynamics. These EN-gained interaction networks are abundantly enriched with human-specific enhancers and SNPs associated with neuropsychiatric disorders, predominantly regulating marker genes of ENs, suggesting a dual role for these enhancers: they not only upregulate gene expression but also play a crucial role in reinforcing the robustness of gene activation. Our findings introduce a dynamic model of gene activation specific to human neurogenesis, orchestrated by loop extrusion and involving species-specific enhancers, providing new perspectives on human brain development, evolution, and neurodevelopmental disorders.

ORGANISM(S): Mus musculus Homo sapiens Macaca mulatta

PROVIDER: GSE267089 | GEO | 2025/11/19

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Although technological advances now allow increased tumor profiling, a detailed understanding of the mechanisms leading to the development of different cancers remains elusive. Our approach towards understanding the molecular events that lead to cancer is to characterize changes in transcriptional regulatory networks between normal and tumor tissue. Because enhancer activity is thought to be critical in regulating cell fate decisions, we have focused our studies on distal regulatory elements and transcription factors that bind to these elements. Using DNA methylation data, we identified more than 25,000 enhancers that are differentially activated in breast, prostate, and kidney tumor tissues, as compared to normal tissues. We then developed an analytical approach called TENET (Tracing Enhancer Networks using Epigenetic Traits) that correlates DNA methylation levels at enhancers with gene expression to identify more than 800,000 genome-wide links from enhancers to genes and from genes to enhancers. We found more than 1,200 transcription factors to be involved in these tumor-specific enhancer networks. We further characterized several transcription factors linked to a large number of enhancers in each tumor type, including GATA3 in non-basal breast tumors, HOXC6 and DLX1 in prostate tumors, and ZNF395 in kidney tumors. We showed that HOXC6 and DLX1 are associated with different clusters of prostate tumor-specific enhancers and confer distinct transcriptomic changes upon knockdown in C42B prostate cancer cells. We also discovered de novo motifs enriched in enhancers linked to ZNF395 in kidney tumors. Our studies characterized tumor-specific enhancers and revealed key transcription factors involved in enhancer networks for specific tumor types and subgroups. Our findings, which include a large set of identified enhancers and transcription factors linked to those enhancers in breast, prostate, and kidney cancers, will facilitate understanding of enhancer networks and mechanisms leading to the development of these cancers. Examination of FAIRE and ChIP assays in prostate and breast epithelial cells. RNA-seq assays in C42B, prostate cancer cell line after knocking down of TFs (HOXC6, DLX1).

Dataset Information

SCOPE-C Reveals the Key Role of Long-Range Loop Extrusion in Dynamic Enhancer Networks for Robust Gene Activation in Human Fetal Cortical Neurogenesis

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets