Evidence map›Paper›PMID 37808741›Full record

ArticlebioRxiv : the preprint server for biology2023

5-hydroxymethylcytosines regulate gene expression as a passive DNA demethylation resisting epigenetic mark in proliferative somatic cells.

Alex Wei, Hongjie Zhang, Qi Qiu, Emily B Fabyanic, Peng Hu, Hao Wu

Open access · greenAbstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed, 4 citations in OpenAlex.

  1. Article
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

6 authors at 2 institutions in 2 countries.

Alex WeiDepartment of Genetics, University of Pennsylvania, Philadelphia, PA 19104.
Hongjie ZhangDepartment of Genetics, University of Pennsylvania, Philadelphia, PA 19104.
Qi QiuDepartment of Genetics, University of Pennsylvania, Philadelphia, PA 19104.
Emily B FabyanicDepartment of Genetics, University of Pennsylvania, Philadelphia, PA 19104.
Peng HuDepartment of Genetics, University of Pennsylvania, Philadelphia, PA 19104.
Hao WuDepartment of Genetics, University of Pennsylvania, Philadelphia, PA 19104.
University of Pennsylvania · USShanghai Ocean University · CN

Funding

Defining causal roles of genomic variants on gene regulatory networks with spatiotemporally-resolved single-cell multiomicsU01HG012047 · NHGRI · UNIVERSITY OF PENNSYLVANIA · PI HONGJUN SONG, Hao Wu · 2021 to 2026
$7.1M
Ultra low-input epigenetic sequencing with combined enzymatic and long-read technologiesR01HG010646 · NHGRI · UNIVERSITY OF PENNSYLVANIA · PI Gang Fang, Rahul Manu Kohli · 2019 to 2026
$3.9M
Dissecting Gene Regulatory Roles of TET Enzymes and 5-hydroxymethylcytosine in Mammalian Active DNA DemethylationF31HG011429 · NHGRI · UNIVERSITY OF PENNSYLVANIA · PI WEI, ALEX TIANJIUN · 2020 to 2022
$118k
NHGRI NIH HHS F31 HG011429NHGRI NIH HHS R01 HG010646NHGRI NIH HHS U01 HG012047
6 · The paper itself

Abstract

Enzymatic erasure of DNA methylation in mammals involves iterative 5-methylcytosine (5mC) oxidation by the ten-eleven translocation (TET) family of DNA dioxygenase proteins. As the most abundant form of oxidized 5mC, the prevailing model considers 5-hydroxymethylcytosine (5hmC) as a key nexus in active DNA demethylation that can either indirectly facilitate replication-dependent depletion of 5mC by inhibiting maintenance DNA methylation machinery (UHRF1/DNMT1), or directly be iteratively oxidized to 5-formylcytosine (5fC) and 5-carboxycytosine (5caC) and restored to cytosine (C) through thymine DNA glycosylase (TDG)-mediated 5fC/5caC excision repair. In proliferative somatic cells, to what extent TET-dependent removal of 5mC entails indirect DNA demethylation via 5hmC-induced replication-dependent dilution or direct iterative conversion of 5hmC to 5fC/5caC is unclear. Here we leverage a catalytic processivity stalling variant of human TET1 (TET1.var: T1662E) to decouple the stepwise generation of 5hmC from subsequent 5fC/5caC generation, excision and repair. By using a CRISPR/dCas9-based epigenome-editing platform, we demonstrate that 5fC/5caC excision repair (by wild-type TET1, TET1.wt), but not 5hmC generation alone (by TET1.var), is requisite for robust restoration of unmodified cytosines and reversal of somatic silencing of the methylation-sensitive, germline-specific

Identifiers

PMID37808741
PMCPMC10557716
OpenAlexW4387138089

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.