Evidence map›Paper›PMID 25106691›Full record

ArticleBMC genomics2014

5-hydroxymethylcytosine represses the activity of enhancers in embryonic stem cells: a new epigenetic signature for gene regulation.

Inchan Choi, Rinho Kim, Hee-Woong Lim, Klaus H Kaestner, Kyoung-Jae Won

Open access · goldAbstract read
In one paragraph

Article in BMC genomics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.4field-weighted citation impact, top 11% of its field
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

22 citing papers in PubMed, 42 citations in OpenAlex.

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  12. Epigenetics and Trained Immunity.Antioxidants & redox signaling · 2018
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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

5 authors at 1 institution in 1 country.

Inchan Choi
Rinho Kim
Hee-Woong Lim
Klaus H KaestnerDepartment of Genetics, Institute for Diabetes, Obesity and Metabolism, University of Pennsylvania, 3400 Civic Center Blvd, 19104 Philadelphia, PA, USA. kaestner@mail.med.upenn.edu.
Kyoung-Jae Won
University of Pennsylvania · US

Funding

VIRAL VECTOR COREP30DK019525 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI MITCHELL A. LAZAR · 1986 to 2026
$48.3M
Regulatory cascades in gastrointestinal proliferationR37DK053839 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI KAESTNER, KLAUS H · 2012 to 2021
$3.8M
An Integrative Approach to Construct a Regulatory Network Effected by TDZsR21DK098769 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI WON, KYOUNG JAE · 2013 to 2014
$440k
NIDDK NIH HHS DK 19525NIDDK NIH HHS P30 DK019525NIDDK NIH HHS P30-DK19525NIDDK NIH HHS R21 DK098769NIDDK NIH HHS R21DK098769-01NIDDK NIH HHS R37 DK053839
6 · The paper itself

Abstract

backgroundRecent mapping of 5-hydroxymethylcytosine (5hmC) provides a genome-wide view of the distribution of this important chromatin mark. However, the role of 5hmC in specific regulatory regions is not clear, especially at enhancers.

resultsWe found a group of distal transcription factor binding sites highly enriched for 5-hdroxymethylcytosine (5hmC), but lacking any known activating histone marks and being depleted for nascent transcripts, suggesting a repressive role for 5hmC in mouse embryonic stem cells (mESCs). 5-formylcytosine (5fC), which is known to mark poised enhancers where H3K4me1 is enriched, is also observed at these sites. Furthermore, the 5hmC levels were inversely correlated with RNA polymerase II (PolII) occupancy in mESCs as well as in fully differentiated adipocytes. Interestingly, activating H3K4me1/2 histone marks were enriched at these sites when the associated genes become activated following lineage specification. These putative enhancers were shown to be functional in embryonic stem cells when unmethylated. Together, these data suggest that 5hmC suppresses the activity of this group of enhancers, which we termed "silenced enhancers".

conclusionsOur findings indicate that 5hmC has a repressive role at specific proximal and distal regulatory regions in mESCs, and suggest that 5hmC is a new epigenetic mark for silenced enhancers.

Indexed as

Epigenesis, Genetic5-MethylcytosineAnimalsBinding SitesCell LineageCytosineEmbryonic Stem CellsEnhancer Elements, GeneticHistonesMiceRNA, MessengerTranscription Factors5-hydroxymethylcytosine5-MethylcytosineCytosineHistonesRNA, MessengerTranscription Factors

Identifiers

PMID25106691
PMCPMC4133056
OpenAlexW2081021899

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.