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Cited by 2Epigenetics and DNA MethylationGenomics and Chromatin DynamicsCancer-related gene regulation

IPMK depletion influences genome-wide DNA methylation

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Sin, Zachary, Kinnear, Evan, Doshi, Raj, Chatterjee, Sujan, Derbel, Houssemeddine, Guha, Prasun, Liu, Qian·2025·Biochemical and Biophysical Research Communications
DOI 10.1016/j.bbrc.2025.151874PMC PMC12685546
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Abstract

Inositol polyphosphate multikinase (IPMK) is emerging as a critical regulator of nuclear functions. While earlier studies in yeast and cell lines linked IPMK to gene expression, recent work reveals its role in modulating histone acetylation through the activation of histone deacetylases 1/3 (HDAC1/3). Interestingly, HDAC1/3 interact with DNA methyltransferase 1 (DNMT1), stabilizing DNMT1 and promoting DNA methylation. As an HDAC1/3 activator, IPMK may thereby influence DNA methylation dynamics. This study investigates how the genetic depletion of IPMK influences DNA methylation, though the role of its kinase activity remains untested. Using long-read Oxford nanopore sequencing, we conducted methylation analysis for >28 millions of CpG sites and discovered that IPMK deletion results in over 22,000 differentially methylated regions (DMRs). Integrating affected genes by DMRs and RNA-seq data, we found that 35 genes show an inverse correlation between methylation in promoter regions and gene expression. Pathway analysis revealed that genes related to tissue remodeling and hematopoiesis are affected. Notably, MMP14 and LIF showed significant methylation changes in promoter regions under IPMK deletion, resulting in decreased mRNA and protein expression. Collectively, this study identifies IPMK as a novel regulator of DNA methylation. While this study did not investigate the role of IPMK's kinase activity in regulating DNA methylation, future studies will determine whether IPMK's effects on DNA methylation are driven by its kinase activity or by kinase-independent mechanisms.

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Authors
Sin, Z., Kinnear, E., Doshi, R., Chatterjee, S., Derbel, H., Guha, P., & Liu, Q.
Affiliations
University of Nevada, Las Vegas (US)
Corresponding author
  • Guha, Prasun
  • Liu, Qian
ORCID
Venue
Biochemical and Biophysical Research Communications
Publisher
Elsevier BV
Published
2025-06
Volume
766
Pages
151874
ISSN
0006-291X (ISSN-L)
DOI
10.1016/j.bbrc.2025.151874
PMC
PMC12685546
OpenAlex
W4409654803
Cited by
2
References
2
Citations by year
2026: 1 · 2025: 1
FWCI
0.60
Type
journal article
Language
en
Open access
Licence
Locations
  • Biochemical and Biophysical Research Communications (acceptedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion)
Funders
  • University of Nevada Las Vegas
  • National Institutes of Health
  • University of Nevada, Reno
  • NIH National Institute of General Medical Sciences (R16GM154726)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer-related gene regulation
Keywords
inositol polyphosphate multikinase, DNA methylation, differentially methylated regions, DNMT1, promoter methylation, gene expression, tissue remodeling, hematopoiesis, MMP-14, LiF, kinase activity
MeSH terms
Humans, Promoter Regions, Genetic, Phosphotransferases (Alcohol Group Acceptor), CpG Islands, DNA Methylation

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