Evidence map›Paper›PMID 32973041›Full record

ArticleGenome research2020

Identification of determinants of differential chromatin accessibility through a massively parallel genome-integrated reporter assay.

Jennifer Hammelman, Konstantin Krismer, Budhaditya Banerjee, David K Gifford, Richard I Sherwood

Open access · bronzeAbstract read
In one paragraph

Article in Genome research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing 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

13 citing papers in PubMed, 24 citations in OpenAlex.

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  13. Using CRISPR to understand and manipulate gene regulation.Development (Cambridge, England) · 2021
    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.

Jennifer HammelmanComputational and Systems Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Konstantin KrismerComputer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Budhaditya BanerjeeDivision of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
David K GiffordComputer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Richard I SherwoodDivision of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Massachusetts Institute of Technology · USBrigham and Women's Hospital · US

Funding

Graduate Training in Computational and Systems BiologyT32GM087237 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BURGE, CHRISTOPHER B · 2009 to 2023
$4.6M
High-Throughput Native Context Mapping and Modeling of Regulatory DNAR01HG008754 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GIFFORD, DAVID K · 2016 to 2019
$2.7M
High-throughput methods for elucidating the control of chromatin accessibilityR01HG008363 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GIFFORD, DAVID K · 2015 to 2017
$2.3M
Distal enhancers controlling motor neuron gene expression programR01NS109217 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI WICHTERLE, HYNEK · 2019 to 2022
$2.1M
Predictive transcription factor modeling to program endodermal cell fatesK01DK101684 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI SHERWOOD, RICHARD I · 2014 to 2018
$670k
NHGRI NIH HHS R01 HG008363NHGRI NIH HHS R01 HG008754NIDDK NIH HHS K01 DK101684NIGMS NIH HHS T32 GM087237NINDS NIH HHS R01 NS109217
6 · The paper itself

Abstract

A key mechanism in cellular regulation is the ability of the transcriptional machinery to physically access DNA. Transcription factors interact with DNA to alter the accessibility of chromatin, which enables changes to gene expression during development or disease or as a response to environmental stimuli. However, the regulation of DNA accessibility via the recruitment of transcription factors is difficult to study in the context of the native genome because every genomic site is distinct in multiple ways. Here we introduce the multiplexed integrated accessibility assay (MIAA), an assay that measures chromatin accessibility of synthetic oligonucleotide sequence libraries integrated into a controlled genomic context with low native accessibility. We apply MIAA to measure the effects of sequence motifs on cell type-specific accessibility between mouse embryonic stem cells and embryonic stem cell-derived definitive endoderm cells, screening 7905 distinct DNA sequences. MIAA recapitulates differential accessibility patterns of 100-nt sequences derived from natively differential genomic regions, identifying E-box motifs common to epithelial-mesenchymal transition driver transcription factors in stem cell-specific accessible regions that become repressed in endoderm. We show that a single binding motif for a key regulatory transcription factor is sufficient to open chromatin, and classify sets of stem cell-specific, endoderm-specific, and shared accessibility-modifying transcription factor motifs. We also show that overexpression of two definitive endoderm transcription factors,

Indexed as

Regulatory Sequences, Nucleic AcidAnimalsBase CompositionChromatinDNAEmbryonic Stem CellsEndodermGenomicsMiceNucleotide MotifsOligonucleotidesSequence Analysis, DNATranscription FactorsChromatinDNAOligonucleotidesTranscription Factors

Identifiers

PMID32973041
PMCPMC7605270
OpenAlexW3088315249

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.