Genome-wide quantification of the effects of DNA methylation on human gene regulation.
Elife
; 72018 12 21.
Article
em En
| MEDLINE
| ID: mdl-30575519
ABSTRACT
Changes in DNA methylation are involved in development, disease, and the response to environmental conditions. However, not all regulatory elements are functionally methylation-dependent (MD). Here, we report a method, mSTARR-seq, that assesses the causal effects of DNA methylation on regulatory activity at hundreds of thousands of fragments (millions of CpG sites) simultaneously. Using mSTARR-seq, we identify thousands of MD regulatory elements in the human genome. MD activity is partially predictable using sequence and chromatin state information, and distinct transcription factors are associated with higher activity in unmethylated versus methylated DNA. Further, pioneer TFs linked to higher activity in the methylated state appear to drive demethylation of experimentally methylated sites. MD regulatory elements also predict methylation-gene expression relationships across individuals, where they are 1.6x enriched among sites with strong negative correlations. mSTARR-seq thus provides a map of MD regulatory activity in the human genome and facilitates interpretation of differential methylation studies.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Cromatina
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Genoma Humano
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Análise de Sequência de DNA
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Metilação de DNA
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Epigênese Genética
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Elife
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Estados Unidos