Evidence map›Paper›PMID 36379931›Full record

ArticleNature communications2022

High-affinity chromodomains engineered for improved detection of histone methylation and enhanced CRISPR-based gene repression.

G Veggiani, R Villaseñor, G D Martyn, J Q Tang, M W Krone, J Gu, C Chen, M L Waters, K H Pearce, T Baubec and 1 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.1field-weighted citation impact, top 23% 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

7 citing papers in PubMed, 14 citations in OpenAlex.

  1. Review
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  6. Contribution of Electrostatic CHJournal of the American Chemical Society · 2024
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 5 institutions in 5 countries.

G VeggianiThe Anvil Institute, Kitchener, ON, N2G 1H6, Canada. gveggiani@lsu.edu.ORCID 0000-0002-4064-0112
R Villaseñor *Division of Molecular Biology, Biomedical Center Munich, Ludwig-Maximilians-University, 82152, Planegg-Martinsried, Germany.ORCID 0000-0002-3644-9817
G D Martyn *The Anvil Institute, Kitchener, ON, N2G 1H6, Canada.ORCID 0000-0002-7373-7834
J Q TangThe Anvil Institute, Kitchener, ON, N2G 1H6, Canada.ORCID 0000-0002-6802-6325
M W KroneDepartment of Chemistry, University of North Carolina at Chapel Hill, CB 3290, Chapel Hill, NC, 27599, USA.ORCID 0000-0002-8602-3742
J GuThe Anvil Institute, Kitchener, ON, N2G 1H6, Canada.
C ChenThe Anvil Institute, Kitchener, ON, N2G 1H6, Canada.
M L WatersDepartment of Chemistry, University of North Carolina at Chapel Hill, CB 3290, Chapel Hill, NC, 27599, USA.ORCID 0000-0002-4917-5755
K H PearceCenter for Integrative Chemical Biology and Drug Discovery, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.ORCID 0000-0001-8138-5421
T BaubecDepartment of Molecular Mechanisms of Disease, University of Zurich, 8057, Zurich, Switzerland.ORCID 0000-0001-8474-6587
S S SidhuThe Anvil Institute, Kitchener, ON, N2G 1H6, Canada. sachdev.sidhu@uwaterloo.ca.ORCID 0000-0001-7755-5918
University of North Carolina at Chapel Hill · USUniversity of Waterloo · CALouisiana State University · USUniversity of Zurich · CHUtrecht University · NL

Funding

Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI David Darr · 1985 to 2026
$201.5M
NIH Administrative Supplement to Purchase a LyophilizerR35GM145227 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI MARCEY L WATERS · 2022 to 2026
$2.2M
Origins of Ligand Binding and Selectivity in Methyllysine Reader and Writer ProteinsR01GM118499 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI WATERS, MARCEY L · 2017 to 2022
$1.6M
NCI NIH HHS P30 CA016086NIGMS NIH HHS R01 GM118499NIGMS NIH HHS R35 GM145227
6 · The paper itself

Abstract

Histone methylation is an important post-translational modification that plays a crucial role in regulating cellular functions, and its dysregulation is implicated in cancer and developmental defects. Therefore, systematic characterization of histone methylation is necessary to elucidate complex biological processes, identify biomarkers, and ultimately, enable drug discovery. Studying histone methylation relies on the use of antibodies, but these suffer from lot-to-lot variation, are costly, and cannot be used in live cells. Chromatin-modification reader domains are potential affinity reagents for methylated histones, but their application is limited by their modest affinities. We used phage display to identify key residues that greatly enhance the affinities of Cbx chromodomains for methylated histone marks and develop a general strategy for enhancing the affinity of chromodomains of the human Cbx protein family. Our strategy allows us to develop powerful probes for genome-wide binding analysis and live-cell imaging. Furthermore, we use optimized chromodomains to develop extremely potent CRISPR-based repressors for tailored gene silencing. Our results highlight the power of engineered chromodomains for analyzing protein interaction networks involving chromatin and represent a modular platform for efficient gene silencing.

Indexed as

HistonesLysineChromatinHumansMethylationProtein Processing, Post-TranslationalChromatinHistonesLysine

Identifiers

PMID36379931
PMCPMC9666628
OpenAlexW4309437992

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.