GEO series

Conserved Cis-Acting Range Extender Elements Mediate Long-Range Developmental Enhancer Activity in Mammals

GSE243635 Mus musculus (mouse) ChIP-seq / ATAC-seq (genome binding and open chromatin) 13 samples Submitted 2024/05/28 Platform GPL24247

At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · mouse · 13 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: Mus musculus (mouse)
Samples: 13 samples: 13 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; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper: Conserved Cis-Acting Range Extender Element Mediates Extreme Long-Range Enhancer Activity in MammalsbioRxiv : the preprint server for biology · 2024

Summary (written by the submitters)

Long-range developmental enhancers can regulate cell-type specific target gene expression over distances that exceed hundreds of thousands of base pairs in mammals. Although higher-order chromatin organization provides support for such long-range enhancer—promoter interactions, the genetic factors that regulate these interactions during mammalian development remain largely unexplored.

Read the full summary ↓

To address this central question, we replaced a limb enhancer, located >800,000 base pairs from its target promoter, with equivalent limb enhancers of similar strength from other genomic loci. We used this replacement strategy to generate six knock-in mouse strains, with enhancers from four distinct genomic loci. All enhancers drove strong expression in developing limb buds when placed adjacent to a reporter gene. However, when transplanted to a distal location, all four enhancers failed to activate remote gene expression and distal limb outgrowth, suggesting that proximally-active enhancers cannot activate transcription remotely. Including a highly conserved, but previously uncharacterized, sequence found adjacent to a long-range limb enhancer rescued gene expression and limb outgrowth. This cis-acting Range EXtender (REX) element does not have classical enhancer activity but is necessary and sufficient for enhancer–promoter communication over very long distances in vivo. The REX element contains highly conserved [C/T]AATTA consensus sequences that match binding preferences of LIM-homeodomain (LHX) transcription factors. We used multiomic single-cell ATAC-seq/RNA-seq profiling to identify [C/T]AATTA homeodomain motifs next to thousands of long-range limb enhancers. The presence of these motifs positively correlates with E–P distance genome-wide. Our data support a model where REX elements facilitate target gene activation by remote enhancers over very long distances in mammalian genomes.

Published in

Conserved Cis-Acting Range Extender Element Mediates Extreme Long-Range Enhancer Activity in Mammals

Bower G, Hollingsworth EW, Jacinto S et al. · bioRxiv : the preprint server for biology 2024 · PMID 38826394 · doi:10.1101/2024.05.26.595809

This dataset

Open GSE243635 in finder → Find more mouse RNA-seq 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 GSE243635_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 PRJNA1019308 and SRA study SRP462013. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 38826394) ↗

Study design

13 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 13 sample titles: 13 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

GSM7792090 Hindlimb, E11.5, snRNA
GSM7792091 Hindlimb, E11.5, ATAC-seq
GSM7792092 ZRS/LacZ Hindlimb ZPA, E11.5, replicate 1, ATAC-seq
GSM7792093 ZRS/LacZ Hindlimb ZPA, E11.5, replicate 2, ATAC-seq
GSM7792094 ZRS/LacZ Hindlimb ZPA, E11.5, replicate 3, ATAC-seq
GSM7792095 ZRS/hs72 Hindlimb ZPA, E11.5, replicate 1, ATAC-seq
GSM7792096 ZRS/hs72 Hindlimb ZPA, E11.5, replicate 2, ATAC-seq
GSM7792097 ZRS/hs72 Hindlimb ZPA, E11.5, replicate 3, ATAC-seq
GSM7792098 ZRS/hs72 Hindlimb ZPA, E11.5, replicate 4, ATAC-seq
GSM7792099 ZRS/hs1516 Hindlimb ZPA, E11.5, replicate 1, ATAC-seq
GSM7792100 ZRS/hs1516 Hindlimb ZPA, E11.5, replicate 2, ATAC-seq
GSM7792101 ZRS/hs1516 Hindlimb ZPA, E11.5, replicate 3, ATAC-seq
GSM7792102 ZRS/hs1516 Hindlimb ZPA, E11.5, replicate 4, ATAC-seq

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GSE309572 MLL2 facilitates long-range gene regulation through LINE1 elements [ChIP-Seq] 89 samples shares long-range, elements
GSE296315 Promoter- and Enhancer-Dependent Cohesin Loading Initiates Chromosome Looping to Fold Tcrb Loci for Long-Range Recombination 81 samples shares long-range, enhancer
GSE295250 Conserved Noncoding Cis-Elements Associated with Hibernation Modulate Metabolic and Behavioral Adaptations in Mice [RNA-seq] 72 samples shares conserved, elements
GSE256299 Conserved helical motifs in the Ikaros IDR mediate NuRD corepressor interaction and transcriptional repression. 72 samples shares conserved, mediate
GSE295340 Polycomb Chromatin Topology Enables Long-Range Enhancer Recruitment during Craniofacial Development [ChIP-seq] 42 samples shares long-range, enhancer
GSE296305 Promoter- and Enhancer-Dependent Cohesin Loading Initiates Chromosome Looping to Fold Tcrb Loci for Long-Range Recombination [CUT&RUN] 42 samples shares long-range, enhancer

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