Evidence map›Paper›PMID 32178723›Full record

ArticleEpigenetics & chromatin2020

The histone methyltransferase Setd8 alters the chromatin landscape and regulates the expression of key transcription factors during erythroid differentiation.

Jacquelyn A Myers, Tyler Couch, Zachary Murphy, Jeffrey Malik, Michael Getman, Laurie A Steiner

Open access · goldAbstract read
In one paragraph

Article in Epigenetics & chromatin, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

19 citing papers in PubMed, 28 citations in OpenAlex.

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  10. The role(s) of NF-Y in development and differentiation.Cell death and differentiation · 2025
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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

6 authors at 2 institutions in 1 country.

Jacquelyn A MyersCenter for Pediatric Biomedical Research, Department of Pediatrics, University of Rochester, Rochester, NY, USA.
Tyler CouchCenter for Pediatric Biomedical Research, Department of Pediatrics, University of Rochester, Rochester, NY, USA.
Zachary MurphyCenter for Pediatric Biomedical Research, Department of Pediatrics, University of Rochester, Rochester, NY, USA.
Jeffrey MalikCenter for Pediatric Biomedical Research, Department of Pediatrics, University of Rochester, Rochester, NY, USA.
Michael GetmanCenter for Pediatric Biomedical Research, Department of Pediatrics, University of Rochester, Rochester, NY, USA.
Laurie A SteinerCenter for Pediatric Biomedical Research, Department of Pediatrics, University of Rochester, Rochester, NY, USA. Laurie_Steiner@urmc.rochester.edu.ORCID 0000-0002-2923-4105
University of Rochester · USUniversity of Rochester Medical Center · US

Funding

Elucidation of the Role of Setd8 and H4K20me1 in ErythropoiesisR01DK104920 · NIDDK · UNIVERSITY OF ROCHESTER · PI STEINER, LAURIE A. · 2016 to 2024
$3.1M
NIDDK NIH HHS R01 DK104920
6 · The paper itself

Abstract

backgroundSETD8 is the sole methyltransferase capable of mono-methylating histone H4, lysine 20. SETD8 and H4K20me1 play a role in a number of essential biologic processes, including cell cycle progression, establishment of higher order chromatin structure, and transcriptional regulation. SETD8 is highly expressed in erythroid cells and erythroid deletion of Setd8 is embryonic lethal by embryonic day 11.5 (E11.5) due to profound anemia, suggesting that it has an erythroid-specific function. The function of SETD8 in the hemopoietic system is poorly understood. The goal of our study was to gain insights into the function of SETD8 during erythroid differentiation.

resultsWe performed ATAC-seq (assay for transposase-accessible chromatin) on sorted populations of E10.5 Setd8 mutant and control erythroblasts. Accessibility profiles were integrated with expression changes and a mark of heterochromatin (H3K27me3) performed in wild-type E10.5 erythroblasts to further understand the role of SETD8 in erythropoiesis. Data integration identified regions of greater chromatin accessibility in Setd8 mutant cells that co-located with H3K27me3 in wild-type E10.5 erythroblasts suggesting that these regions, and their associated genes, are repressed during normal erythropoiesis. The majority of these more accessible regions were located in promoters and they frequently co-located with the NFY complex. Pathway analysis of genes identified through data integration revealed stemness-related pathways. Among those genes were multiple transcriptional regulators active in multipotent progenitors, but repressed during erythroid differentiation including Hhex, Hlx, and Gata2. Consistent with a role for SETD8 in erythroid specification, SETD8 expression is up-regulated upon erythroid commitment, and Setd8 disruption impairs erythroid colony forming ability.

conclusionTaken together, our results suggest that SETD8 is an important regulator of the chromatin landscape during erythroid differentiation, particularly at promoters. Our results also identify a novel role for Setd8 in the establishment of appropriate patterns of lineage-restricted gene expression during erythroid differentiation.

Indexed as

Chromatin Assembly and DisassemblyErythropoiesisAnimalsCell LineCells, CulturedErythroblastsHistone-Lysine N-MethyltransferaseHumansMiceTranscription FactorsHistone-Lysine N-MethyltransferaseKMT5a protein, mouseTranscription FactorsChromatinDifferentiationErythroidH4K20me1Setd8

Identifiers

PMID32178723
PMCPMC7075014
OpenAlexW3012228043

What OpenQuestion holds

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LicenceCC BY
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.