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Acetyl-CoA production by Mediator-bound 2-ketoacid dehydrogenases boosts de novo histone acetylation and is regulated by nitric oxide [Chipseq_H3K27ac_spikein]

GSE245442 Mus musculus (mouse) ChIP-seq / ATAC-seq (genome binding and open chromatin) 36 samples Submitted 2024/11/19 Platform GPL24247
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · mouse · 36 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
36 samples: 18 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.
Paper
Acetyl-CoA production by Mediator-bound 2-ketoacid dehydrogenases boosts de novo histone acetylation and is regulated by nitric oxideMolecular cell · 2024
Summary (written by the submitters)
Histone modifying enzymes depend on the availability of cofactors, with acetyl-CoA being required for histone acetyltransferase (HAT) activity. The discovery that mitochondrial acyl-CoA producing enzymes are also delivered to the nucleus suggests that high concentrations of metabolites generated locally may impact acetylation of histones and other nuclear substrates and eventually control gene regulation.
Read the full summary ↓
Here we show that 2-ketoacid dehydrogenases were stably associated with the Mediator complex in macrophages, thus providing a local supply of acetyl-CoA and increasing the generation of hyper-acetylated histone tails. Nitric oxide (NO), which is produced in large amounts in LPS-stimulated macrophages, inhibited both the activity of 2-ketoacid dehydrogenases and their association with Mediator. Consequently, NO reduced de novo histone acetylation at genomic regions with high acetyl-CoA deposition rates. Our findings indicate that a local supply of acetyl-CoA generated by Mediator-bound 2-ketoacid dehydrogenases is required to maximize acetylation of histone tails at sites of elevated HAT activity.
Published in
Acetyl-CoA production by Mediator-bound 2-ketoacid dehydrogenases boosts de novo histone acetylation and is regulated by nitric oxide
Russo M, Gualdrini F, Vallelonga V et al. · Molecular cell 2024 · PMID 38242130 · doi:10.1016/j.molcel.2023.12.033
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 GSE245442_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 peak files (.bed, .narrowPeak) and signal tracks (.bigWig) among the supplementary files; the raw reads are on ENA.

Also filed as BioProject PRJNA1028519 and SRA study SRP466506. Searching any of these in the dataset finder brings you back here.

Study design
18 conditions, mostly in duplicate
sh1_MED14_LPS ×2 sh1_MED14_TSA ×2 sh1_MED14_UT ×2 sh2_MED14_LPS ×2 sh2_MED14_TSA ×2 sh2_MED14_UT ×2 shA1_LPS ×2 shA1_NO_LPS ×2 +10 more

Supports a between-group comparison across 36 samples.

How we read this: 18 replicated groups read from 36 sample titles; they account for 36 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
Datasets on a similar topic

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