Evidence map›Paper›PMID 26748519›Full record

ArticleAmerican journal of human genetics2016

Invariant TAD Boundaries Constrain Cell-Type-Specific Looping Interactions between Promoters and Distal Elements around the CFTR Locus.

Emily M Smith, Bryan R Lajoie, Gaurav Jain, Job Dekker

Open access · bronzeAbstract read
In one paragraph

Article in American journal of human genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers.

0numbers the graph read from it
0cells of the map it votes in
97citing papers in PubMed
13.2field-weighted citation impact, top 1% 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

97 citing papers in PubMed, 150 citations in OpenAlex.

  1. Article
  2. Epigenetic regulation and chromatin organization in cystic fibrosis airways.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2026
    Review
  3. Article
  4. Article
  5. bioRxiv : the preprint server for biology · 2025
    Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. International journal of molecular sciences · 2025
    Article
  12. Article
  13. TAD-dependent sub-TAD is required for enhancer-promoter interaction enabling the β-globin transcription.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024
    Article
  14. An atlas of the tomato epigenome reveals that KRYPTONITE shapes TAD-like boundaries through the control of H3K9ac distribution.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  15. Article
  16. Article
  17. Review
  18. Tissue-Specific Regulation ofInternational journal of molecular sciences · 2023
    Review
  19. Article
  20. Review

37 more citing papers are in PubMed but not listed here.

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

4 authors at 2 institutions in 1 country.

Emily M SmithProgram in Systems Biology, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA, 01605-0103, USA.
Bryan R LajoieProgram in Systems Biology, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA, 01605-0103, USA.
Gaurav JainProgram in Systems Biology, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA, 01605-0103, USA.
Job DekkerProgram in Systems Biology, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA, 01605-0103, USA; Howard Hughes Medical Institute. Electronic address: job.dekker@umassmed.edu.
University of Massachusetts Chan Medical School · USHoward Hughes Medical Institute · US

Funding

Structural Annotation of the Human GenomeR01HG003143 · NHGRI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI Job Dekker · 2003 to 2026
$15.4M
A Comprehensive Catalog of Dnasel Hypersensitive SitesU54HG007010 · NHGRI · UNIVERSITY OF WASHINGTON · PI STAMATOYANNOPOULOS, JOHN A · 2012 to 2016
$12.4M
Howard Hughes Medical InstituteNHGRI NIH HHS HG003143NHGRI NIH HHS HG007010NHGRI NIH HHS R01 HG003143NHGRI NIH HHS U54 HG007010
6 · The paper itself

Abstract

Three-dimensional genome structure plays an important role in gene regulation. Globally, chromosomes are organized into active and inactive compartments while, at the gene level, looping interactions connect promoters to regulatory elements. Topologically associating domains (TADs), typically several hundred kilobases in size, form an intermediate level of organization. Major questions include how TADs are formed and how they are related to looping interactions between genes and regulatory elements. Here we performed a focused 5C analysis of a 2.8 Mb chromosome 7 region surrounding CFTR in a panel of cell types. We find that the same TAD boundaries are present in all cell types, indicating that TADs represent a universal chromosome architecture. Furthermore, we find that these TAD boundaries are present irrespective of the expression and looping of genes located between them. In contrast, looping interactions between promoters and regulatory elements are cell-type specific and occur mostly within TADs. This is exemplified by the CFTR promoter that in different cell types interacts with distinct sets of distal cell-type-specific regulatory elements that are all located within the same TAD. Finally, we find that long-range associations between loci located in different TADs are also detected, but these display much lower interaction frequencies than looping interactions within TADs. Interestingly, interactions between TADs are also highly cell-type-specific and often involve loci clustered around TAD boundaries. These data point to key roles of invariant TAD boundaries in constraining as well as mediating cell-type-specific long-range interactions and gene regulation.

Indexed as

Enhancer Elements, GeneticPromoter Regions, GeneticCell LineChromatinCystic Fibrosis Transmembrane Conductance RegulatorHumansCFTR protein, humanChromatinCystic Fibrosis Transmembrane Conductance RegulatorCFTRchromatin loopinggene regulationtopologically associating domain

Identifiers

PMID26748519
PMCPMC4716690
OpenAlexW2223041743

What OpenQuestion holds

Textmetadata
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.