Evidence map›Paper›PMID 33554132›Full record

ArticleCurrent research in structural biology2020

The BRPF1 bromodomain is a molecular reader of di-acetyllysine.

Juliet O Obi, Mulu Y Lubula, Gabriel Cornilescu, Amy Henrickson, Kara McGuire, Chiara M Evans, Margaret Phillips, Samuel P Boyson, Borries Demeler, John L Markley and 1 more

Open access · goldAbstract read
In one paragraph

Article in Current research in structural biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.3field-weighted citation impact, top 20% 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

15 citing papers in PubMed, 22 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. High-Affinity Peptide-Drug Conjugate Ligands for the TRIM24 PHD and Bromodomain.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025
    Article
  5. Article
  6. Article
  7. Article
  8. Epigenetic Causes of Overgrowth Syndromes.The Journal of clinical endocrinology and metabolism · 2024
    Review
  9. Article
  10. Article
  11. Mosaicism inCase reports in genetics · 2023
    Article
  12. Review
  13. Article
  14. Coordination of Di-Acetylated Histone Ligands by the ATAD2 Bromodomain.International journal of molecular sciences · 2021
    Article
  15. 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

11 authors at 3 institutions in 2 countries.

Juliet O ObiDepartment of Pharmaceutical Sciences, Albany College of Pharmacy and Health Sciences, Colchester, VT, 05446, USA.
Mulu Y LubulaDepartment of Pharmaceutical Sciences, Albany College of Pharmacy and Health Sciences, Colchester, VT, 05446, USA.
Gabriel CornilescuNational Magnetic Resonance Facility at Madison and Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, 53706, USA.
Amy HenricksonDepartment of Chemistry and Biochemistry, University of Lethbridge, Lethbridge, Alberta, CA, Canada.
Kara McGuireDepartment of Pharmaceutical Sciences, Albany College of Pharmacy and Health Sciences, Colchester, VT, 05446, USA.
Chiara M EvansDepartment of Pharmaceutical Sciences, Albany College of Pharmacy and Health Sciences, Colchester, VT, 05446, USA.
Margaret PhillipsDepartment of Pharmaceutical Sciences, Albany College of Pharmacy and Health Sciences, Colchester, VT, 05446, USA.
Samuel P BoysonDepartment of Pharmaceutical Sciences, Albany College of Pharmacy and Health Sciences, Colchester, VT, 05446, USA.
Borries DemelerDepartment of Chemistry and Biochemistry, University of Lethbridge, Lethbridge, Alberta, CA, Canada.
John L MarkleyNational Magnetic Resonance Facility at Madison and Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, 53706, USA.
Karen C GlassDepartment of Pharmaceutical Sciences, Albany College of Pharmacy and Health Sciences, Colchester, VT, 05446, USA.
Albany College of Pharmacy and Health Sciences · USUniversity of Lethbridge · CAUniversity of Wisconsin–Madison · US

Funding

TR&D 3: TECHNOLOGY DEVELOPMENT FOR NMR STUDIES OF SMALL MOLECULES (METABOLOMICS, NATURAL PRODUCTS, METABOLITE-PROTEIN INTERACTIONS) pp.537-585 P41GM103399 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI MARKLEY, JOHN LUTE · 2012 to 2019
$9.4M
Development of an UltraScan Meta-Scheduler for HPC Job SubmissionR01GM120600 · NIGMS · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Emre H. Brookes, BORRIES DEMELER · 2016 to 2026
$3.6M
A Large-area Pixel Array Detector System for Macromolecular CrystallographyS10RR028438 · NCRR · STANFORD UNIVERSITY · PI WEIS, WILLIAM I · 2010 to 2010
$2.1M
Integrated state-of-the-art LC-MS/NMR system for the University of WisconsinS10RR025062 · NCRR · UNIVERSITY OF WISCONSIN-MADISON · PI MARKLEY, JOHN LUTE · 2008 to 2008
$1.7M
Mechanisms of chromatin binding and selection by family IV bromodomainsR15GM104865 · NIGMS · ALBANY COLLEGE OF PHARMACY · PI GLASS, KAREN CHAMPAGNE · 2013 to 2016
$910k
Upgrade of the NMRFAM 750 MHz NMR SpectrometerS10RR029220 · NCRR · UNIVERSITY OF WISCONSIN-MADISON · PI MARKLEY, JOHN LUTE · 2010 to 2010
$766k
NMR Spectrometer System Optimized for Direct 13C or 15N DetectionS10RR023438 · NCRR · UNIVERSITY OF WISCONSIN-MADISON · PI MARKLEY, JOHN LUTE · 2008 to 2008
$500k
CONSOLE UPGRADES FOR NMR FACILITYS10RR008438 · NCRR · UNIVERSITY OF WISCONSIN MADISON · PI MARKLEY, JOHN L · 1993 to 1993
–
WIDE-BORE 9.4 TESLA NMR SPECTROMETER FOR UW-MADISONS10RR002781 · NCRR · UNIVERSITY OF WISCONSIN MADISON · PI MARKLEY, JOHN L · 1986 to 1986
–
NCRR NIH HHS S10 RR023438NCRR NIH HHS S10 RR025062NCRR NIH HHS S10 RR028438NCRR NIH HHS S10 RR029220NIGMS NIH HHS P41 GM103399NIGMS NIH HHS R15 GM104865
6 · The paper itself

Abstract

Bromodomain-containing proteins are often part of chromatin-modifying complexes, and their activity can lead to altered expression of genes that drive cancer, inflammation and neurological disorders in humans. Bromodomain-PHD finger protein 1 (BRPF1) is part of the MOZ (monocytic leukemic zinc-finger protein) HAT (histone acetyltransferase) complex, which is associated with chromosomal translocations known to contribute to the development of acute myeloid leukemia (AML). BRPF1 contains a unique combination of chromatin reader domains including two plant homeodomain (PHD) fingers separated by a zinc knuckle (PZP domain), a bromodomain, and a proline-tryptophan-tryptophan-proline (PWWP) domain. BRPF1 is known to recruit the MOZ HAT complex to chromatin by recognizing acetylated lysine residues on the N-terminal histone tail region through its bromodomain. However, histone proteins can contain several acetylation modifications on their N-terminus, and it is unknown how additional marks influence bromodomain recruitment to chromatin. Here, we identify the BRPF1 bromodomain as a selective reader of di-acetyllysine modifications on histone H4. We used ITC assays to characterize the binding of di-acetylated histone ligands to the BRPF1 bromodomain and found that the domain binds preferentially to histone peptides H4K5acK8ac and H4K5acK12ac. Analytical ultracentrifugation (AUC) experiments revealed that the monomeric state of the BRPF1 bromodomain coordinates di-acetylated histone ligands. NMR chemical shift perturbation studies, along with binding and mutational analyses, revealed non-canonical regions of the bromodomain-binding pocket that are important for histone tail recognition. Together, our findings provide critical information on how the combinatorial action of post-translational modifications can modulate BRPF1 bromodomain binding and specificity.

Indexed as

BromodomainDi-acetyllysineEpigeneticsHistonePost-translational modification

Identifiers

PMID33554132
PMCPMC7861561
OpenAlexW3025974179

What OpenQuestion holds

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LicenceCC BY-NC-ND
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 OpenQuestion graph.