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Updated: May 22, 2026

Application of MassSQUIRM for Quantitative Measurements of Lysine Demethylase Activity
07:02

Application of MassSQUIRM for Quantitative Measurements of Lysine Demethylase Activity

Published on: March 11, 2012

Lysine-specific demethylase 2A (KDM2A) normalizes human embryonic stem cell derived keratinocytes

Shiro Iuchi1, Howard Green

  • 1Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.

Proceedings of the National Academy of Sciences of the United States of America
|May 29, 2012
PubMed

Insights

High expression of a specific human lysine-specific demethylase 2A (KDM2A) variant, KDM2A-N782, unexpectedly enhances keratinocyte proliferation, contradicting known demethylase activity. This finding reveals complex, opposing roles for KDM2A isoforms.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • Lysine-specific demethylase 2A (KDM2A) is known to inhibit cell proliferation by reducing gene expression.
  • Human embryonic stem cell-derived Nod keratinocytes exhibit poor proliferation and short lifespan, necessitating strategies for improvement.

Purpose of the Study:

  • To investigate the role of KDM2A in improving the proliferation of hES-cell-derived Nod keratinocytes.
  • To identify specific KDM2A transcripts or isoforms that influence keratinocyte proliferation.

Main Methods:

  • Preparation and analysis of four alternatively spliced KDM2A cDNAs.
  • Expression analysis of KDM2A variants in hES-cell-derived Nod keratinocytes.
  • Assessment of the impact of KDM2A variants on cell proliferation.

Main Results:

  • High expression of the KDM2A gene was found to improve the poor proliferation of Nod keratinocytes.
  • Only one of the four alternatively spliced KDM2A cDNAs, KDM2A-N782, stimulated proliferation.
  • KDM2A-N782 encodes a 782AA protein with JmjC, CXXC, and Ring domains, but lacks F-box and AMN1 domains.

Conclusions:

  • Differentially spliced KDM2A transcripts can lead to opposing cellular outcomes, specifically impacting keratinocyte proliferation.
  • KDM2A exhibits complex and context-dependent activities, with specific isoforms like KDM2A-N782 promoting proliferation.
  • This study presents critical evidence for the multifaceted functions of KDM2A, challenging previous understandings of its role in gene regulation and cell growth.

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