Evidence map›Paper›PMID 38904842›Full record

ArticleMolecular biology reports2024

SETDB1 deletion causes DNA demethylation and upregulation of multiple zinc-finger genes.

Yong-Kook Kang, Jaemin Eom, Byungkuk Min, Jung Sun Park

Abstract read
In one paragraph

Article in Molecular biology reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

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3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

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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

4 authors.

Yong-Kook KangDevelopment and Differentiation Research Center, Aging Convergence Research Center (ACRC), Korea Research Institute of Bioscience Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon, 34141, South Korea. ykkang@kribb.re.kr.
Jaemin EomDevelopment and Differentiation Research Center, Aging Convergence Research Center (ACRC), Korea Research Institute of Bioscience Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon, 34141, South Korea.
Byungkuk MinDevelopment and Differentiation Research Center, Aging Convergence Research Center (ACRC), Korea Research Institute of Bioscience Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon, 34141, South Korea.
Jung Sun ParkDevelopment and Differentiation Research Center, Aging Convergence Research Center (ACRC), Korea Research Institute of Bioscience Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon, 34141, South Korea.

Funding

National Research Council of Science and Technology CRC22013-100National Research Foundation of Korea 2022R1A2C2004374
6 · The paper itself

Abstract

backgroundSETDB1 (SET domain bifurcated-1) is a histone H3-lysine 9 (H3K9)-specific methyltransferase that mediates heterochromatin formation and repression of target genes. Despite the assumed functional link between DNA methylation and SETDB1-mediated H3K9 trimethylations, several studies have shown that SETDB1 operates autonomously of DNA methylation in a region- and cell-specific manner. This study analyzes SETDB1-null HAP1 cells through a linked methylome and transcriptome analysis, intending to explore genes controlled by SETDB1-involved DNA methylation. METHODS AND

resultsWe investigated SETDB1-mediated regulation of DNA methylation and gene transcription in human HAP1 cells using reduced-representation bisulfite sequencing (RRBS) and RNA sequencing. While two-thirds of differentially methylated CpGs (DMCs) in genic regions were hypomethylated in SETDB1-null cells, we detected a plethora of C2H2-type zinc-finger protein genes (C2H2-ZFP, 223 of 749) among the DMC-associated genes. Most C2H2-ZFPs with DMCs in their promoters were found hypomethylated in SETDB1-KO cells, while other non-ZFP genes with promoter DMCs were not. These C2H2-ZFPs with DMCs in their promoters were significantly upregulated in SETDB1-KO cells. Similarly, C2H2-ZFP genes were upregulated in SETDB1-null 293T cells, suggesting that SETDB1's function in ZFP gene repression is widespread. There are several C2H2-ZFP gene clusters on chromosome 19, which were selectively hypomethylated in SETDB1-KO cells.

conclusionsSETDB1 collectively and specifically represses a substantial fraction of the C2H2-ZFP gene family. Through the en-bloc silencing of a set of ZFP genes, SETDB1 may help establish a panel of ZFP proteins that are expressed cell-type specifically and thereby can serve as signature proteins for cellular identity.

Indexed as

DNA MethylationHistone-Lysine N-MethyltransferaseZinc FingersCell LineCpG IslandsDNA DemethylationGene DeletionHistonesHumansPromoter Regions, GeneticUp-RegulationHistone-Lysine N-MethyltransferaseHistonesSETDB1 protein, humanDNA methylationHypermethylationHypomethylationSETDB1Zinc-finger protein

Identifiers

PMID38904842
PMCPMC11192681

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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.