Evidence map›Paper›PMID 41340067›Full record

ArticleEpigenetics & chromatin2025

Developmentally dynamic chromatin state at loci regulating organ crosstalk by remote sensing and signaling.

Aditya Parmar, Sanjay K Nigam, Kun Cai, Kian Falah, Vladimir S Ermakov, Kelly Wang, Cole J Ferguson

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Epigenetics & chromatin, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Aditya Parmar *Department of Pathology, University of California San Diego, 9500 Gilman Dr., San Diego, CA, 92093, USA.
Sanjay K Nigam *Department of Pediatrics, University of California San Diego, 9500 Gilman Dr., San Diego, CA, 92093, USA.
Kun CaiDepartment of Pathology, University of California San Diego, 9500 Gilman Dr., San Diego, CA, 92093, USA.
Kian FalahDepartment of Pediatrics, University of California San Diego, 9500 Gilman Dr., San Diego, CA, 92093, USA.
Vladimir S ErmakovDepartment of Pediatrics, University of California San Diego, 9500 Gilman Dr., San Diego, CA, 92093, USA.
Kelly WangDepartment of Pathology, University of California San Diego, 9500 Gilman Dr., San Diego, CA, 92093, USA.
Cole J FergusonDepartment of Pathology, University of California San Diego, 9500 Gilman Dr., San Diego, CA, 92093, USA. cferguson@health.ucsd.edu.

Funding

The Role of OAT1 in UremiaR01DK109392 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI NIGAM, SANJAY K · 2017 to 2025
$3.8M
Illumina NovaSeq 6000 Sequencing SystemS10OD026929 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JEPSEN, KRISTEN LYNN · 2019 to 2019
$600k
NIDDK NIH HHS R01 DK109392NIDDK NIH HHS R01DK109392NIH HHS S10 OD026929
6 · The paper itself

Abstract

backgroundInterorgan communication, metabolite regulation and drug handling require fine-tuned small molecule transport across membranes. The Remote Sensing and Signaling (RSS) theory, which has found applicability in chronic kidney disease and uric acid disorders, emphasizes the central role of solute carrier (SLC) and ATP-binding cassette (ABC) transporters, enzymes and transcription factors in organ crosstalk. Based on prior network biology studies, ~ 1000 protein-coding genes are predicted to mediate RSS. This gene set largely overlaps with genes that are important for absorption, digestion, metabolism and excretion (ADME) of small molecules. However, it is not known how epigenetic regulation of these loci changes during the development of the liver and kidney, which control the small molecule composition of the blood, or the brain, whose physiology relies upon this process. Epigenetic regulation of these genes is also critical for understanding pharmacokinetics.

resultsWe profiled chromatin state at 1034 RSS/ADME genes in the mouse kidney, liver and brain at the embryonic and adult stages. Using the high-resolution chromatin mapping method CUT&RUN, we examined the activating histone modifications H3K4me3, H3K27ac and H3K9ac, and the repressive modification H3K27me3. Activating modifications were most dynamic at the chromatin level in the liver and least dynamic in the brain. Acetylated histone modifications were more dynamic overall than methylation marks in all three tissues. Hierarchical clustering demonstrated that a subset of RSS/ADME genes undergoes a coordinated program of activation during kidney and liver development that correlates with changes in transcript abundance.

conclusionsDefining the changes in chromatin that occur after birth within this gene set provides insight into tissue-specific regulation of RSS. Our findings carry implications for how the body acquires autonomous functionality through organ crosstalk mediated by transport of endogenous small molecules. Given their critical roles in ADME as well as handling of exogenous toxins, medications and metabolites derived from the gut microbiome, our analysis has ramifications for both precision pharmacology and diseases such as chronic kidney disease, metabolic syndrome and gout, in which dysregulation of RSS drives pathophysiology.

Indexed as

ChromatinKidneyLiverAnimalsBrainEpigenesis, GeneticGene Expression Regulation, DevelopmentalHistonesMiceSignal TransductionChromatinHistonesABC transportersADME genesChromatinEpigeneticsEpigenomicsRemote sensing and signaling theorySLC transporters

Identifiers

PMID41340067
PMCPMC12720468

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.