Methylation of a CGATA element inhibits binding and regulation by GATA-1.
Nat Commun
; 11(1): 2560, 2020 05 22.
Article
em En
| MEDLINE
| ID: mdl-32444652
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Elementos de Resposta
/
Fator de Transcrição GATA1
Limite:
Animals
Idioma:
En
Revista:
Nat Commun
Ano de publicação:
2020
Tipo de documento:
Article