Methylation of a CGATA element inhibits binding and regulation by GATA-1

Lu Yang, Zhiliang Chen, Elizabeth S. Stout, Fabien Delerue, Lars M. Ittner, Marc R. Wilkins, Kate G. R. Quinlan and Merlin Crossley ()
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Lu Yang: School of Biotechnology and Biomolecular Sciences, UNSW Sydney
Zhiliang Chen: School of Biotechnology and Biomolecular Sciences, UNSW Sydney
Elizabeth S. Stout: School of Biotechnology and Biomolecular Sciences, UNSW Sydney
Fabien Delerue: Macquarie University
Lars M. Ittner: Macquarie University
Marc R. Wilkins: School of Biotechnology and Biomolecular Sciences, UNSW Sydney
Kate G. R. Quinlan: School of Biotechnology and Biomolecular Sciences, UNSW Sydney
Merlin Crossley: School of Biotechnology and Biomolecular Sciences, UNSW Sydney

Nature Communications, 2020, vol. 11, issue 1, 1-10

Abstract: Abstract Alterations in DNA methylation occur during development, but the mechanisms by which they influence gene expression remain uncertain. There are few examples where modification of a single CpG dinucleotide directly affects transcription factor binding and regulation of a target gene in vivo. Here, we show that the erythroid transcription factor GATA-1 — that typically binds T/AGATA sites — can also recognise CGATA elements, but only if the CpG dinucleotide is unmethylated. We focus on a single CGATA site in the c-Kit gene which progressively becomes unmethylated during haematopoiesis. We observe that methylation attenuates GATA-1 binding and gene regulation in cell lines. In mice, converting the CGATA element to a TGATA site that cannot be methylated leads to accumulation of megakaryocyte-erythroid progenitors. Thus, the CpG dinucleotide is essential for normal erythropoiesis and this study illustrates how a single methylated CpG can directly affect transcription factor binding and cellular regulation.

Date: 2020
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DOI: 10.1038/s41467-020-16388-1

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