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Evolutionary guided transcription factor design programs novel T cell states [ChIP-Seq]

GSE335058 Homo sapiens (human) ChIP-seq / ATAC-seq (genome binding and open chromatin) 66 samples Submitted 2026/06/17 Platform GPL34284
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 66 samples

What it is
ChIP-seq / ATAC-seq (genome binding and open chromatin)Where proteins bind the genome, or which regions are open and active.
Organism
Homo sapiens (human)
Samples
66 samples: 22 conditions, mostly in duplicateGroups 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; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Summary (written by the submitters)
Human protein-coding genes evolved via modular rearrangement of domains from ancestral genes. Here, we develop a scalable, evolutionarily guided method to assemble novel protein-coding genes from constituent domains within a protein family, termed DESynR (Domain Engineered via Synthesis and Recombination) genes. Using primary human chimeric antigen receptor T cells as a model, we find that the expression of DESynR Activator Protein-1 (AP-1) transcription factors (TFs) significantly outperforms the overexpression of natural AP-1 TFs in multiple functional assays in vitro and in vivo.
Read the full summary ↓
Top DESynR AP-1 TFs exhibit non-intuitive domain architectures, including from TFs not canonically expressed in T cells. DESynR AP-1 TFs induce broad transcriptional and epigenetic reprogramming and establish non-natural T cell states that optimize features of exhaustion, effector and cytotoxic function, and persistence— in some cases co-opting gene expression modules from disparate cell types. We show that this reprogramming is primarily driven by differential regulation of established AP-1-bound regulatory elements, rather than unique binding. Finally, we extend the DESynR methodology to Erythroblast Transformation Specific (ETS) and Forkhead box (FOX) TFs to support the generalizability across protein families. Overall, we demonstrate that novel configurations of existing protein domains may uncover non-evolved genes that program cell states with therapeutic relevance.
This dataset
Open GSE335058 in finder → Find more human ChIP / ATAC / CUT&Tag datasets →
Download · which file do I need?

Direct links to NCBI and ENA, 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.

Series matrix ↓
2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE335058_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓
3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: Look for peak files (.bed, .narrowPeak) and signal tracks (.bigWig) among the supplementary files; the raw reads are on ENA.

Also filed as BioProject PRJNA1477198 and SRA study SRP708628. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
22 conditions, mostly in duplicate
Healthy human donor (3), CAR T cells, JUN-FOS… ×2 Healthy human donor (3), CAR T cells, JUN-FOS… ×2 Healthy human donor (3), CAR T cells, JUN, Ch… ×2 Healthy human donor (3), CAR T cells, JUN, In… ×2 Healthy human donor (3), CAR T cells, FOS, Ch… ×2 Healthy human donor (3), CAR T cells, FOS, In… ×2 Healthy human donor (3), CAR T cells, BATF, C… ×2 Healthy human donor (3), CAR T cells, BATF, I… ×2 +36 more

Supports a between-group comparison across 44 samples.

How we read this: 22 replicated groups read from 66 sample titles; they account for 44 of them. 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

+ 26 more — browse all 66 samples with per-sample file links →

Datasets on a similar topic

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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.