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

14 Citations (Scopus)
13 Downloads (Pure)

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.

Original languageEnglish
Article number2560
Pages (from-to)1-10
Number of pages10
JournalNature Communications
Volume11
Issue number1
DOIs
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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