Evidence map›Paper›PMID 39579767›Full record

ArticleMolecular cell2024

Multiple allelic configurations govern long-range Shh enhancer-promoter communication in the embryonic forebrain.

Jailynn Harke, Jeewon R Lee, Son C Nguyen, Arian Arab, Staci M Rakowiecki, Siewert Hugelier, Christina Paliou, Antonella Rauseo, Rebecca Yunker, Kellen Xu and 5 more

Abstract read
In one paragraph

Article in Molecular cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. 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

15 authors.

Jailynn HarkeDepartment of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Penn Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Jeewon R LeeDepartment of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Son C NguyenDepartment of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Penn Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Arian ArabPenn Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Staci M RakowieckiDepartment of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Siewert HugelierDepartment of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Christina PaliouAndalusian Center for Developmental Biology (CABD), Spanish National Research Council, Pablo de Olavide University, Andalusian Regional Government, Seville, Spain.
Antonella RauseoDepartment of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland; Institute of Genetics and Genomics in Geneva (iGE3), University of Geneva, Geneva, Switzerland.
Rebecca YunkerDepartment of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Penn Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Kellen XuDepartment of Pharmacology, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, Piscataway, NJ, USA.
Yao YaoDepartment of Animal and Dairy Science, Regenerative Bioscience Center, University of Georgia, Athens, GA, USA.
Melike LakadamyaliPenn Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Guillaume AndreyDepartment of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland; Institute of Genetics and Genomics in Geneva (iGE3), University of Geneva, Geneva, Switzerland.
Douglas J EpsteinDepartment of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: epsteind@pennmedicine.upenn.edu.
Eric F JoyceDepartment of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Penn Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: erjoyce@upenn.edu.

Funding

TRANSCRIPTIONAL CONTROL OF SONIC HEDGEHOG SIGNALINGR01NS039421 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI EPSTEIN, DOUGLAS J · 2000 to 2023
$8.5M
PREDOCTORAL TRAINING PROGRAM IN GENETICST32GM008216 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI EPSTEIN, DOUGLAS J · 1987 to 2023
$8.3M
THYROID HORMONE RECEPTORS--REGULATION AND FUNCTIONR01DK043806 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI MITCHELL A. LAZAR · 1991 to 2026
$4.9M
Regulation of chromatin folding in space and timeR35GM128903 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI Eric F. Joyce · 2018 to 2026
$4.2M
Single-cell dissection of chromatin architecture mechanisms connecting pathologic instability and transcriptional silencingU01DA052715 · NIDA · UNIVERSITY OF PENNSYLVANIA · PI JAIN, RAJAN, JOYCE, ERIC F. · 2020 to 2024
$3.1M
Single-cell analysis of 3D genome organization in senescent cellsR01AG082437 · NIA · UNIVERSITY OF PENNSYLVANIA · PI Rajan Jain, Eric F. Joyce · 2024 to 2026
$1.9M
Probing the three-dimensional organization of enhancer-promoter communicationF31HD103375 · NICHD · UNIVERSITY OF PENNSYLVANIA · PI HARKE, JAILYNN ALYSE · 2020 to 2022
$126k
NIA NIH HHS R01 AG082437NICHD NIH HHS F31 HD103375NIDA NIH HHS U01 DA052715NIDDK NIH HHS R01 DK043806NIGMS NIH HHS R35 GM128903NIGMS NIH HHS T32 GM008216NINDS NIH HHS R01 NS039421
6 · The paper itself

Abstract

Developmental gene regulation requires input from enhancers spread over large genomic distances. Our understanding of long-range enhancer-promoter (E-P) communication, characterized as loops, remains incomplete without addressing the role of intervening chromatin. Here, we examine the topology of the entire Sonic hedgehog (Shh) regulatory domain in individual alleles from the mouse embryonic forebrain. Through sequential Oligopaint labeling and super-resolution microscopy, we find that the Shh locus maintains a compact structure that adopts several diverse configurations independent of Shh expression. The most frequent configuration contained distal E-P contacts at the expense of those more proximal to Shh, consistent with an interconnected loop. Genetic perturbations demonstrate that this long-range E-P communication operates by Shh-expression-independent and dependent mechanisms, involving CTCF binding sites and active enhancers, respectively. We propose a model whereby gene regulatory elements secure long-range E-P interactions amid an inherent architectural framework to coordinate spatiotemporal patterns of gene expression.

Indexed as

AllelesEnhancer Elements, GeneticGene Expression Regulation, DevelopmentalHedgehog ProteinsPromoter Regions, GeneticProsencephalonAnimalsBinding SitesCCCTC-Binding FactorChromatinMiceCCCTC-Binding FactorChromatinCtcf protein, mouseHedgehog ProteinsShh protein, mouse3D genome organizationallelic configurationsCTCFdevelopmental gene regulationenhancer activityenhancer-promoter communicationE-Psequential DNA-FISHShhsuper-resolution microscopy

Identifiers

PMID39579767
PMCPMC11663103

What OpenQuestion holds

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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.