Histone Demethylase Kdm2a Regulates Germ Cell Genes and Endogenous Retroviruses in Embryonic Stem Cells

Abstract

Aim: To investigate the function of Kdm2a in embryonic stem cells (ESCs). Materials & methods: Expression profile analysis after Kdm2a knockout. Analysis of Kdm2a, H3K4me3 and H3K27me3 ChIP-seq data in ESCs. qPCR analysis and ChIP-qPCR analysis of epigenetic changes after Kdm2a loss. Results:Kdm2a was dispensable for pluripotency maintenance in ESCs. Kdm2a genomic binding profile was positively correlated with that of H3K4me3, Zfx and Tet1. Kdm2a directly regulated germ cell genes in primordial germ cell-like cells. Kdm2a loss led to the reduced expression of endogenous retrovirus IAPEy and resulted in the gain of H3K36me2 and loss of H3K4me3 on IAPEy. Conclusion: Kdm2a regulates germ cell genes and endogenous retroviruses in ESCs possibly through demethylating H3K36me2 and influencing H3K4me3 deposition.

Keywords::

• embryonic stem cell
• endogenous retrovirus
• histone demethylase
• Kdm2a

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/full/10.2217/epi-2018-0126

Acknowledgments

The authors thank Beijing Genomics Institute for providing high-throughput sequencing service. The authors also thank J Ji for her technical assistance.

Financial & competing interests disclosure

This work was supported by China Key Research and Development Program (2018YFA0107000); the National Science Foundation of China under 31671352; the Natural Science Foundation of Tianjin City (15JCZDJC65600); the National Thousand Young Talents Program, and the Fundamental Research Funds for the Central Universities. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This work was supported by China Key Research and Development Program (2018YFA0107000); the National Science Foundation of China under 31671352; the Natural Science Foundation of Tianjin City (15JCZDJC65600); the National Thousand Young Talents Program, and the Fundamental Research Funds for the Central Universities. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.