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, Merlin Crossley*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)
5 Downloads (Pure)


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.

Original languageEnglish
Article number2560
Pages (from-to)1-10
Number of pages10
JournalNature Communications
Issue number1
Publication statusPublished - 22 May 2020

Bibliographical note

Copyright the Author(s) 2020. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.


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