Evidence map›Paper›PMID 39253426›Full record

ArticlebioRxiv : the preprint server for biology2024

Temporally discordant chromatin accessibility and DNA demethylation define short and long-term enhancer regulation during cell fate specification.

Lindsey N Guerin, Timothy J Scott, Jacqueline A Yap, Annelie Johansson, Fabio Puddu, Tom Charlesworth, Yilin Yang, Alan J Simmons, Ken S Lau, Rebecca A Ihrie and 1 more

Abstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Lindsey N GuerinDepartment of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, USA.ORCID 0000-0002-2070-4481
Timothy J ScottDepartment of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, USA.
Jacqueline A YapDepartment of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, USA.
Annelie Johanssonbiomodal, Chesterford Research Park, Cambridge, UK.
Fabio Puddubiomodal, Chesterford Research Park, Cambridge, UK.
Tom Charlesworthbiomodal, Chesterford Research Park, Cambridge, UK.
Yilin YangDepartment of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, USA.ORCID 0009-0000-9869-4044
Alan J SimmonsDepartment of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, USA.
Ken S LauDepartment of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, USA.ORCID 0000-0001-8438-0319
Rebecca A IhrieDepartment of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, USA.ORCID 0000-0003-0439-0141
Emily HodgesDepartment of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, USA.ORCID 0000-0001-6513-610X

Funding

Shaping the Microenvironment by DPEP1 Facilitates Adenoma ProgressionU54CA274367 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Bhuminder Singh · 2022 to 2026
$9.7M
Tuft cell heterogeneity in function, lineage, and structure in ileal inflammatory diseaseR01DK103831 · NIDDK · VANDERBILT UNIVERSITY · PI LAU, KEN S · 2016 to 2024
$4.4M
Identifying mTOR Dependent Periods During Brain DevelopmentR01NS118580 · NINDS · VANDERBILT UNIVERSITY · PI ESS, KEVIN C, IHRIE, REBECCA A · 2020 to 2024
$2.1M
Decoding genome function with DNA methylation and human phenome dataR01GM147078 · NIGMS · VANDERBILT UNIVERSITY · PI Emily Hodges · 2022 to 2026
$1.9M
NCI NIH HHS U54 CA274367NIDDK NIH HHS R01 DK103831NIGMS NIH HHS R01 GM147078NINDS NIH HHS R01 NS118580
6 · The paper itself

Abstract

Epigenetic mechanisms govern the transcriptional activity of lineage-specifying enhancers; but recent work challenges the dogma that joint chromatin accessibility and DNA demethylation are prerequisites for transcription. To understand this paradox, we established a highly-resolved timeline of DNA demethylation, chromatin accessibility, and transcription factor occupancy during neural progenitor cell differentiation. We show thousands of enhancers undergo rapid, transient accessibility changes associated with distinct periods of transcription factor expression. However, most DNA methylation changes are unidirectional and delayed relative to chromatin dynamics, creating transiently discordant epigenetic states. Genome-wide detection of 5-hydroxymethylcytosine further revealed active demethylation begins ahead of chromatin and transcription factor activity, while enhancer hypomethylation persists long after these activities have dissipated. We demonstrate that these timepoint specific methylation states predict past, present and future chromatin accessibility using machine learning models. Thus, chromatin and DNA methylation collaborate on different timescales to mediate short and long-term enhancer regulation during cell fate specification.

Indexed as

5-hydroxymethylation6-base sequencingATAC-MeChromatin AccessibilityDifferentiationDNA MethylationEnhancersEpigeneticsMachine LearningNeural Progenitor Cells

Identifiers

PMID39253426
PMCPMC11383056

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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 OpenQuestion graph.