Evidence map›Paper›PMID 36069349›Full record

ArticleMolecular systems biology2022

Changes in chromatin accessibility are not concordant with transcriptional changes for single-factor perturbations.

Karun Kiani, Eric M Sanford, Yogesh Goyal, Arjun Raj

Open access · goldAbstract read
In one paragraph

Article in Molecular systems biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed
6.5field-weighted citation impact, top 2% 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

62 citing papers in PubMed, 80 citations in OpenAlex.

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  9. Differential Wnt/β-catenin signaling via TCF7L2/LEF1 binding specificity shapes cellular and tumor phenotypes.Proceedings of the National Academy of Sciences of the United States of America · 2026
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2 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.

Karun KianiGenetics and Epigenetics, Cell and Molecular Biology Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Eric M SanfordGenomics and Computational Biology Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Yogesh GoyalDepartment of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Arjun RajDepartment of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA.ORCID 0000-0002-2915-6960
University of Pennsylvania · USNorthwestern University · US

Funding

UNIVERSITY OF PENNSYLVANIA CAN CTR SUPPORT GRANTP30CA016520 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Robert H. Vonderheide · 1985 to 2026
$222.3M
Targeting exosomal PDL1 to improve immunotherapyP50CA261608 · NCI · WISTAR INSTITUTE · PI VILLANUEVA, JESSIE · 2021 to 2025
$11.3M
Targeted Combination Therapy for MelanomaP50CA174523 · NCI · WISTAR INSTITUTE · PI HERLYN, MEENHARD F · 2014 to 2018
$11.1M
PREDOCTORAL TRAINING PROGRAM IN GENETICST32GM008216 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI EPSTEIN, DOUGLAS J · 1987 to 2023
$8.3M
Decoding the bridges and barriers to cellular reprogramming and lineage identityR01GM137425 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI JAIN, RAJAN, RAJ, ARJUN · 2019 to 2023
$5.6M
A plasticity and reprogramming paradigm for therapy resistance at the single cell levelU01CA227550 · NCI · UNIVERSITY OF PENNSYLVANIA · PI RADHAKRISHNAN, RAVI, RAJ, ARJUN · 2018 to 2022
$3.3M
An integrated approach to melanoma metastasis and therapy resistance: effects of age-related changes in the ECM and the biomechanics of the skinR01CA232256 · NCI · WISTAR INSTITUTE · PI CUKIERMAN, EDNA, RAJ, ARJUN · 2019 to 2023
$3.0M
Understanding and Overcoming Resistance to BRAF/MEK Kinase Inhibitors in MelanomaR01CA238237 · NCI · UNIVERSITY OF PENNSYLVANIA · PI HERLYN, MEENHARD F, RAJ, ARJUN · 2020 to 2024
$2.9M
How does a gene integrate multiple signals?F30HG010986 · NHGRI · UNIVERSITY OF PENNSYLVANIA · PI SANFORD, ERIC · 2020 to 2020
$33k
NCI NIH HHS P30 CA016520NCI NIH HHS P50 CA174523NCI NIH HHS P50 CA261608NCI NIH HHS R01 CA232256NCI NIH HHS R01 CA238237NCI NIH HHS U01 CA227550NHGRI NIH HHS F30 HG010986NIGMS NIH HHS R01 GM137425NIGMS NIH HHS T32 GM008216
6 · The paper itself

Abstract

A major goal in the field of transcriptional regulation is the mapping of changes in the binding of transcription factors to the resultant changes in gene expression. Recently, methods for measuring chromatin accessibility have enabled us to measure changes in accessibility across the genome, which are thought to correspond to transcription factor-binding events. In concert with RNA-sequencing, these data in principle enable such mappings; however, few studies have looked at their concordance over short-duration treatments with specific perturbations. Here, we used tandem, bulk ATAC-seq, and RNA-seq measurements from MCF-7 breast carcinoma cells to systematically evaluate the concordance between changes in accessibility and changes in expression in response to retinoic acid and TGF-β. We found two classes of genes whose expression showed a significant change: those that showed some changes in the accessibility of nearby chromatin, and those that showed virtually no change despite strong changes in expression. The peaks associated with genes in the former group had lower baseline accessibility prior to exposure to signal. Focusing the analysis specifically on peaks with motifs for transcription factors associated with retinoic acid and TGF-β signaling did not reduce the lack of correspondence. Analysis of paired chromatin accessibility and gene expression data from distinct paths along the hematopoietic differentiation trajectory showed a much stronger correspondence, suggesting that the multifactorial biological processes associated with differentiation may lead to changes in chromatin accessibility that reflect rather than driving altered transcriptional status. Together, these results show many gene expression changes can happen independently of changes in the accessibility of local chromatin in the context of a single-factor perturbation.

Indexed as

ChromatinChromatin Immunoprecipitation SequencingTranscription FactorsTransforming Growth Factor betaTretinoinChromatinTranscription FactorsTransforming Growth Factor betaTretinoinchromatin accessibilitygene regulationmulti-omics integrationRNA-seq and ATAC-seq concordancesignal response

Identifiers

PMID36069349
PMCPMC9450098
OpenAlexW4294916217

What Socratic holds

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LicenceCC BY
Read underepoch 390

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 Socratic graph.