Evidence map›Paper›PMID 37024975›Full record

ArticleEpigenetics & chromatin2023

Multilevel interrogation of H3.3 reveals a primordial role in transcription regulation.

Syed Nabeel-Shah, Jyoti Garg, Kanwal Ashraf, Renu Jeyapala, Hyunmin Lee, Alexandra Petrova, James D Burns, Shuye Pu, Zhaolei Zhang, Jack F Greenblatt and 3 more

Open access · goldAbstract read
In one paragraph

Article in Epigenetics & chromatin, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.5field-weighted citation impact, top 34% 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

3 citing papers in PubMed, 3 citations in OpenAlex.

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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

13 authors at 4 institutions in 1 country.

Syed Nabeel-Shah *Department of Chemistry and Biology, Toronto Metropolitan University, 350 Victoria St, Toronto, M5B 2K3, Canada.
Jyoti Garg *Department of Chemistry and Biology, Toronto Metropolitan University, 350 Victoria St, Toronto, M5B 2K3, Canada.
Kanwal AshrafDepartment of Biology, York University, 4700 Keele St, Toronto, M3J 1P3, Canada.
Renu JeyapalaDepartment of Chemistry and Biology, Toronto Metropolitan University, 350 Victoria St, Toronto, M5B 2K3, Canada.
Hyunmin LeeDonnelly Centre, University of Toronto, Toronto, M5S 3E1, Canada.
Alexandra PetrovaDepartment of Chemistry and Biology, Toronto Metropolitan University, 350 Victoria St, Toronto, M5B 2K3, Canada.
James D BurnsDonnelly Centre, University of Toronto, Toronto, M5S 3E1, Canada.
Shuye PuDonnelly Centre, University of Toronto, Toronto, M5S 3E1, Canada.
Zhaolei ZhangDonnelly Centre, University of Toronto, Toronto, M5S 3E1, Canada.
Jack F GreenblattDonnelly Centre, University of Toronto, Toronto, M5S 3E1, Canada.
Ronald E PearlmanDepartment of Biology, York University, 4700 Keele St, Toronto, M3J 1P3, Canada.
Jean-Philippe LambertDepartment of Molecular Medicine, Cancer Research Center, Big Data Research Center, Université Laval, Quebec City, QC, Canada.
Jeffrey FillinghamDepartment of Chemistry and Biology, Toronto Metropolitan University, 350 Victoria St, Toronto, M5B 2K3, Canada. jeffrey.fillingham@torontomu.ca.
University of Toronto · CAToronto Metropolitan University · CAYork University · CAUniversité Laval · CA

Funding

CIHR FDN-154338CIHR MOP13347
6 · The paper itself

Abstract

backgroundEukaryotic cells can rapidly adjust their transcriptional profile in response to molecular needs. Such dynamic regulation is, in part, achieved through epigenetic modifications and selective incorporation of histone variants into chromatin. H3.3 is the ancestral H3 variant with key roles in regulating chromatin states and transcription. Although H3.3 has been well studied in metazoans, information regarding the assembly of H3.3 onto chromatin and its possible role in transcription regulation remain poorly documented outside of Opisthokonts.

resultsWe used the nuclear dimorphic ciliate protozoan, Tetrahymena thermophila, to investigate the dynamics of H3 variant function in evolutionarily divergent eukaryotes. Functional proteomics and immunofluorescence analyses of H3.1 and H3.3 revealed a highly conserved role for Nrp1 and Asf1 histone chaperones in nuclear influx of histones. Cac2, a putative subunit of H3.1 deposition complex CAF1, is not required for growth, whereas the expression of the putative ortholog of the H3.3-specific chaperone Hir1 is essential in Tetrahymena. Our results indicate that Cac2 and Hir1 have distinct localization patterns during different stages of the Tetrahymena life cycle and suggest that Cac2 might be dispensable for chromatin assembly. ChIP-seq experiments in growing Tetrahymena show H3.3 enrichment over the promoters, gene bodies, and transcription termination sites of highly transcribed genes. H3.3 knockout followed by RNA-seq reveals large-scale transcriptional alterations in functionally important genes.

conclusionOur results provide an evolutionary perspective on H3.3's conserved role in maintaining the transcriptional landscape of cells and on the emergence of specialized chromatin assembly pathways.

Indexed as

Gene Expression RegulationHistonesCell NucleusChromatinTranscription, GeneticChromatinHistonesAsf1CAF1ChromatinEpigeneticsFunctional proteomicsH3.3HIRAHistone variantNASPRBBP4/7Tetrahymena

Identifiers

PMID37024975
PMCPMC10080907
OpenAlexW4362692675

What OpenQuestion holds

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LicenceCC BY
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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.