GEO series
Non-CG DNA methylation and MeCP2 stabilize repeated tuning of long genes that distinguish closely related neuron types [RNA-seq]
GSE237084
Mus musculus (mouse)
DNA methylation
38 samples
Submitted 2025/01/31
Platform GPL19057Platform GPL21493
At a glance
DNA methylation · mouse · 38 samples
- What it is
- DNA methylationChemical marks on DNA that help switch genes on or off.
- Organism
- Mus musculus (mouse)
- Samples
- 38 samples: 38 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.
Summary (written by the submitters)
The extraordinary diversity of neuron types in the mammalian brain is delineated at the highest resolution by subtle gene expression differences that may require specialized molecular mechanisms to be maintained. Neurons uniquely express the longest genes in the genome and utilize neuron-enriched non-CG DNA methylation (mCA) together with the Rett syndrome protein, MeCP2, to control gene expression, but the function of these unique gene structures and machinery in regulating finely resolved neuron type-specific gene programs has not been explored.
Read the full summary ↓
Here, we employ epigenomic and spatial transcriptomic analyses to discover a major role for mCA and MeCP2 in maintaining neuron type-specific gene programs that define high resolution cell types. We uncover differential susceptibility to MeCP2 loss in neuronal populations depending on global mCA levels and dissect methylation patterns and intragenic enhancer repression that drive overlapping and distinct gene regulation between neuron types. Strikingly, we show that mCA and MeCP2 regulate genes that are repeatedly tuned to differentiate neuron types at high cellular resolution, including spatially resolved, vision-dependent gene programs in the visual cortex. These repeatedly tuned genes display genomic characteristics, including long length, numerous intragenic enhancers, and enrichment for mCA, that predispose them to regulation by MeCP2. Thus, long gene regulation by the MeCP2 pathway maintains differential gene expression between closely-related neurons to facilitate the exceptional cellular diversity in the brain.
This dataset
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.
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 GSE237084_RAW.tar (it can run to tens of gigabytes).
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.
What the files usually look like: Look for beta-value tables or raw IDAT files among the supplementary files.
Also filed as BioProject PRJNA993684 and SRA study SRP453470. Searching any of these in the dataset finder brings you back here.
Study design
38 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 38 sample titles: 38 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
- GSM7594495 L4, IP1, WT, Gabel, 156-1, GTACACCT, S2, R1, 001
- GSM7594496 L4, IP2, WT, Gabel, 178-3, TACATCGG, S5, R1, 001
- GSM7594497 L4, IP3, WT, Gabel, 244-4, CCAACACT, S7, R1, 001
- GSM7594498 L4, IP4, WT, Gabel, 338-6, TCTAGGAG, S8, R1, 001
- GSM7594499 L4, IP1, KO, Gabel, 156-3, ACGAGAAC, S3, R1, 001
- GSM7594500 L4, IP2, KO, Gabel, 178-1, CGACCTAA, S4, R1, 001
- GSM7594501 L4, IP3, KO, Gabel, 244-3, ATCGTCTC, S6, R1, 001
- GSM7594502 L4, IP4, KO, Gabel, 338-7, CTCGAACA, S9, R1, 001
- GSM7594503 L5, IP1, WT, Gabel, 653-7, IP, AACTCGGA, S5, R1, 001
- GSM7594504 L5, IP2, WT, Gabel, 653-5, IP, AATCCAGC, S3, R1, 001
- GSM7594505 L5, IP3, WT, Gabel, 676-4, IP, GCACACAA, S9, R1, 001
- GSM7594506 L5, IP4, WT, Gabel, 681-3, IP, CTCCTAGT, S10, R1, 001
- GSM7594507 L5, IP1, KO, Gabel, 653-4, IP, CGCTACAT, S2, R1, 001
- GSM7594508 L5, IP2, KO, Gabel, 653-6, IP, CGTCTAAC, S4, R1, 001
- GSM7594509 L5, IP3, KO, Gabel, 676-3, IP, ATGACAGG, S8, R1, 001
- GSM7594510 L5, IP4, KO, Gabel, 681-5, IP, TCTTCGAC, S11, R1, 001
- GSM7594511 L5, Input3, WT, Gabel, 676-4, N, ACTCCTAC, S13, R1, 001
- GSM7594512 L5, Input3, KO, Gabel, 676-3, N, GACTACGA, S12, R1, 001
- GSM7594513 PV, IP1, WT, 586, run, 2916, s, 1, withindex, sequence.txt, CGCTACAT
- GSM7594514 PV, IP2, WT, 594, run, 2916, s, 1, withindex, sequence.txt, CGTCTAAC
- GSM7594515 PV, IP3, 598, wt, run, 2916, s, 1, withindex, sequence.txt, GTCGAGAA
- GSM7594516 PV, IP4, WT, 602, run, 2916, s, 1, withindex, sequence.txt, ATGACAGG
- GSM7594517 PV, IP1, KO, 587, run, 2916, s, 1, withindex, sequence.txt, AATCCAGC
- GSM7594518 PV, IP2, KO, 597, run, 2916, s, 1, withindex, sequence.txt, AACTCGGA
- GSM7594519 PV, IP3, KO, 600, run, 2916, s, 1, withindex, sequence.txt, ACAACAGC
- GSM7594520 PV, IP4, KO, 603, run, 2916, s, 1, withindex, sequence.txt, GCACACAA
- GSM7594521 PV, Input3, WT, 598, run, 2916, s, 1, withindex, sequence.txt, CGTCCATT
- GSM7594522 PV, Input3, KO, 600, run, 2916, s, 1, withindex, sequence.txt, AACTTGCC
- GSM7594523 SST, IP1, WT, Gabel, 637, A01, CGCTACATAT, S2, R1, 001
- GSM7594524 SST, IP2, WT, Gabel, 734, D01, AACTCGGAAT, S5, R1, 001
- GSM7594525 SST, IP3, WT, Gabel, 796, F01, ACAACAGCAT, S7, R1, 001
- GSM7594526 SST, IP4, WT, Gabel, 333-5, H01, GCACACAAAT, S9, R1, 001
- GSM7594527 SST, IP1, KO, Gabel, 638, B01, AATCCAGCAT, S3, R1, 001
- GSM7594528 SST, IP2, KO, Gabel, 733, C01, CGTCTAACAT, S4, R1, 001
- GSM7594529 SST, IP3, KO, Gabel, 795, E01, GTCGAGAAAT, S6, R1, 001
- GSM7594530 SST, IP4, KO, Gabel, 333-4, G01, ATGACAGGAT, S8, R1, 001
- GSM7594531 run, 2916, s, 1, withindex, sequence.txt, ACGAGAAC
- GSM7594532 run, 2916, s, 1, withindex, sequence.txt, GTACACCT
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