Evidence map›Paper›PMID 32687896›Full record

ArticleDevelopmental biology2020

Conjugated activation of myocardial-specific transcription of Gja5 by a pair of Nkx2-5-Shox2 co-responsive elements.

Tianfang Yang, Zhen Huang, Hua Li, Linyan Wang, YiPing Chen

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In one paragraph

Article in Developmental biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.2field-weighted citation impact, top 50% 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

4 citing papers in PubMed, 4 citations in OpenAlex.

  1. Article
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  4. Review
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 2 institutions in 2 countries.

Tianfang YangDepartment of Cell and Molecular Biology, Tulane University, New Orleans, LA, 70118, USA.
Zhen HuangDepartment of Cell and Molecular Biology, Tulane University, New Orleans, LA, 70118, USA; Southern Center for Biomedical Research and Fujian Key Laboratory of Developmental and Neural Biology College of Life Sciences, Fujian Normal University, Fuzhou, Fujian Province, 350108, PR China.
Hua LiDepartment of Cell and Molecular Biology, Tulane University, New Orleans, LA, 70118, USA; Southern Center for Biomedical Research and Fujian Key Laboratory of Developmental and Neural Biology College of Life Sciences, Fujian Normal University, Fuzhou, Fujian Province, 350108, PR China.
Linyan WangDepartment of Cell and Molecular Biology, Tulane University, New Orleans, LA, 70118, USA; State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Preventive Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan Province, 610041, PR China.
YiPing ChenDepartment of Cell and Molecular Biology, Tulane University, New Orleans, LA, 70118, USA. Electronic address: ychen@tulane.edu.
Tulane University · USFujian Normal University · CN

Funding

Genetic and transcription regulation of cardiac pacemaker fateR01HL136326 · NHLBI · TULANE UNIVERSITY OF LOUISIANA · PI CHEN, YIPING · 2017 to 2020
$1.5M
NHLBI NIH HHS R01 HL136326
6 · The paper itself

Abstract

The sinoatrial node (SAN) is the primary pacemaker in the heart. During cardiogenesis, Shox2 and Nkx2-5 are co-expressed in the junction domain of the SAN and regulate pacemaker cell fate through a Shox2-Nkx2-5 antagonism. Cx40 is a marker of working myocardium and an Nkx2-5 transcriptional output antagonized by Shox2, but the underlying regulatory mechanisms remain elusive. Here we characterized a bona fide myocardial-specific Gja5 (coding gene of Cx40) distal enhancer consisting of a pair of Nkx2-5 and Shox2 co-bound elements in the regulatory region of Gja5. Transgenic reporter assays revealed that neither element alone, but the conjugation of both elements together, drives myocardial-specific transcription. Genetic analyses confirmed that the activation of this enhancer depends on Nkx2-5 but is inhibited by Shox2 in vivo, and its presence is essential for Gja5 expression in the myocardium but not the endothelial cells of the heart. Furthermore, chromatin conformation analysis showed an Nkx2-5-dependent loop formation between these two elements and the Gja5 promoter in vivo, indicating that Nkx2-5 bridges the conjugated activation of this enhancer by pairing the two elements to the Gja5 promoter.

Indexed as

Promoter Regions, GeneticTranscription, GeneticAnimalsConnexinsGene Expression Regulation, DevelopmentalHomeobox Protein Nkx-2.5Homeodomain ProteinsMiceMice, TransgenicMyocardiumSinoatrial NodeConnexinsHomeobox Protein Nkx-2.5Homeodomain ProteinsNkx2-5 protein, mouseShox2 protein, mouseEnhancerGja5MyocardiumNkx2-5Shox2Sinoatrial node

Identifiers

PMID32687896
PMCPMC7484358
OpenAlexW3043780554

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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 OpenQuestion graph.