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. 2020 May 22;11:2560. doi: 10.1038/s41467-020-16388-1

Fig. 6. Model to show role of DNA methylation and impact of forced demethylation at the CGATA site in c-Kit intron 2 on haematopoiesis.

Fig. 6

In wild type mice, the CGATA site at intron 2 of c-Kit gene is highly methylated at early stages of haematopoiesis and gradually becomes de-methylated during haematopoiesis. GATA-1 binds to the CGATA site at intron 2 of the c-Kit gene when it is de-methylated and represses the expression of c-Kit. In mutant mice, the (C > T)GATA mutation is unable to be modified by DNA methylation and GATA-1 can bind to this site at earlier stages of haematopoiesis. We observe a decrease in c-Kit expression and an increase in MEP cell number in mice homozygous for this c-Kit (C > T)GATA mutation. Note that the diagram illustrates that methylation of the CGATA element is required for normal regulation of c-Kit but is not likely to be sufficient for the full regulation of the c-Kit gene. Other GATA elements in additional regulatory elements are also likely to be relevant but for brevity are not included here.