KDM2 proteins constrain transcription from CpG island gene promoters independently of their histone demethylase activity.
Nucleic Acids Res
; 47(17): 9005-9023, 2019 09 26.
Article
em En
| MEDLINE
| ID: mdl-31363749
ABSTRACT
CpG islands (CGIs) are associated with the majority of mammalian gene promoters and function to recruit chromatin modifying enzymes. It has therefore been proposed that CGIs regulate gene expression through chromatin-based mechanisms, however in most cases this has not been directly tested. Here, we reveal that the histone H3 lysine 36 (H3K36) demethylase activity of the CGI-binding KDM2 proteins contributes only modestly to the H3K36me2-depleted state at CGI-associated gene promoters and is dispensable for normal gene expression. Instead, we discover that KDM2 proteins play a widespread and demethylase-independent role in constraining gene expression from CGI-associated gene promoters. We further show that KDM2 proteins shape RNA Polymerase II occupancy but not chromatin accessibility at CGI-associated promoters. Together this reveals a demethylase-independent role for KDM2 proteins in transcriptional repression and uncovers a new function for CGIs in constraining gene expression.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Transcrição Gênica
/
Histonas
/
Regiões Promotoras Genéticas
/
Ilhas de CpG
/
Proteínas F-Box
/
Histona Desmetilases com o Domínio Jumonji
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article