Evidence map›Paper›PMID 38870936›Full record

ArticleMolecular cell2024

An autoinhibitory switch of the LSD1 disordered region controls enhancer silencing.

Amanda L Waterbury, Hui Si Kwok, Ceejay Lee, Domenic N Narducci, Allyson M Freedy, Cindy Su, Shaunak Raval, Andrew H Reiter, William Hawkins, Kwangwoon Lee and 8 more

Abstract read
PubMed Full text at PMC Publisher
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 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing 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

10 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. State-of-the-Art and Future Directions in Structural Proteomics.Molecular & cellular proteomics : MCP · 2025
    Review
  5. Article
  6. Article
  7. Review
  8. Review
  9. Article
  10. 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

18 authors.

Amanda L WaterburyDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Hui Si KwokDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Ceejay LeeDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Domenic N NarducciBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, Cambridge, MA 02139, USA.
Allyson M FreedyDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Cindy SuDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Shaunak RavalBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Andrew H ReiterBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
William HawkinsBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Kwangwoon LeeDivision of Genetics, Department of Medicine, Brigham and Women's Hospital, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Jiaming LiDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Samuel M HoenigDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Michael E VinyardBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Philip A ColeDivision of Genetics, Department of Medicine, Brigham and Women's Hospital, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Anders S HansenBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, Cambridge, MA 02139, USA.
Steven A CarrBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Malvina PapanastasiouBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Brian B LiauDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. Electronic address: liau@chemistry.harvard.edu.

Funding

Center for 3D Structure and Physics of the GenomeUM1HG011536 · NHGRI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI DEKKER, JOB, MIRNY, LEONID A · 2020 to 2024
$11.8M
Mapping Structure-Activity Relationships of Chemical Inhibitors via Genome-EditingDP2GM137494 · NIGMS · HARVARD UNIVERSITY · PI LIAU, BRIAN · 2019 to 2019
$2.5M
DYNAMIC BOTTOM-UP DISSECTION OF CHROMATIN LOOPING AND GENE REGULATIONDP2GM140938 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI HANSEN, ANDERS SEJR · 2020 to 2020
$2.3M
Chemical Genetic Approaches to Study Chromatin ComplexesR01CA274437 · NCI · HARVARD UNIVERSITY · PI Brian Liau · 2023 to 2026
$2.2M
Chemical Approaches to Understanding Reversible Lysine ModificationsR35GM149229 · NIGMS · BRIGHAM AND WOMEN'S HOSPITAL · PI PHILIP A COLE · 2023 to 2026
$1.9M
NCI NIH HHS R01 CA274437NHGRI NIH HHS UM1 HG011536NIGMS NIH HHS DP2 GM137494NIGMS NIH HHS DP2 GM140938NIGMS NIH HHS R35 GM149229
6 · The paper itself

Abstract

Transcriptional coregulators and transcription factors (TFs) contain intrinsically disordered regions (IDRs) that are critical for their association and function in gene regulation. More recently, IDRs have been shown to promote multivalent protein-protein interactions between coregulators and TFs to drive their association into condensates. By contrast, here we demonstrate how the IDR of the corepressor LSD1 excludes TF association, acting as a dynamic conformational switch that tunes repression of active cis-regulatory elements. Hydrogen-deuterium exchange shows that the LSD1 IDR interconverts between transient open and closed conformational states, the latter of which inhibits partitioning of the protein's structured domains with TF condensates. This autoinhibitory switch controls leukemic differentiation by modulating repression of active cis-regulatory elements bound by LSD1 and master hematopoietic TFs. Together, these studies unveil alternative mechanisms by which disordered regions and their dynamic crosstalk with structured regions can shape coregulator-TF interactions to control cis-regulatory landscapes and cell fate.

Indexed as

Enhancer Elements, GeneticHistone DemethylasesAnimalsCell DifferentiationGene SilencingHumansIntrinsically Disordered ProteinsMiceProtein BindingTranscription FactorsHistone DemethylasesIntrinsically Disordered ProteinsKDM1A protein, humanTranscription Factorsautoinhibitory switchcondensateintrinsically disordered regionleukemic differentiationtranscriptional corepressortranscription factors

Identifiers

PMID38870936
PMCPMC11193646

What OpenQuestion holds

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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.