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Systematic decoding of cis gene regulation defines context-dependent control of the multi-gene costimulatory receptor locus in human T cells [CRISPRi]

GSE261330 Homo sapiens (human) Other 28 samples Submitted 2024/03/24 Platform GPL18573
At a glance

human · 28 samples

Organism
Homo sapiens (human)
Samples
28 samples: 28 samples, each with a distinct title — no replicated groupsGroups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI.
Paper
Systematic decoding of cis gene regulation defines context-dependent control of the multi-gene costimulatory receptor locus in human T cellsNature genetics · 2024
Summary (written by the submitters)
Cis-regulatory elements (CRE) interact with trans regulators to orchestrate gene expression, but how transcriptional regulation is coordinated in multi-gene loci has not been experimentally defined. We sought to characterize the CREs controlling dynamic expression of adjacent T cell costimulatory genes CD28, CTLA4, and ICOS encoding regulators of cell-mediated immunity.
Read the full summary ↓
Tiling CRISPR interference (CRISPRi) screens in primary human T cells – both Conventional and Regulatory subsets – uncovered gene-, cell subset- and stimulation-specific CREs. Integrating these data with CRISPR knockout (KO) screens and ATAC-seq characterization identified trans regulators influencing chromatin states at specific CRISPRi-responsive elements to control costimulatory gene expression. Lastly, we discovered and extensively validated a critical CTCF boundary that governs this locus, serving to reinforce CRE interaction with CTLA4 while also preventing promiscuous activation of CD28. By systematically mapping CREs and associated trans regulators directly in primary human T cell subsets, this work overcomes longstanding experimental limitations to decode context-dependent gene regulatory programs in a complex, multi-gene locus critical to immune homeostasis.
Published in
Systematic decoding of cis gene regulation defines context-dependent control of the multi-gene costimulatory receptor locus in human T cells
Mowery CT, Freimer JW, Chen Z et al. · Nature genetics 2024 · PMID 38811842 · doi:10.1038/s41588-024-01743-5
This dataset
Download · which file do I need?

Direct links to NCBI, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need.

All supplementary files ↗
3 · The original raw files

Whole study · RAW.tar

Everything the authors deposited as one archive (GSE261330_RAW.tar), including the raw array or instrument files. Can be large; the picker in step 2 takes just the samples you need.

Also filed as BioProject PRJNA1086507. Searching any of these in the dataset finder brings you back here.

Study design
28 samples, each with a distinct title — no replicated groups

Any grouping that defines a comparison lives in the sample characteristics, which GEO records separately from the titles.

How we read this: Read from 28 sample titles: 28 distinct titles with little repetition. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study
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