Chromatin dysregulation associated with NSD1 mutation in head and neck squamous cell carcinoma.
Cell Rep
; 34(8): 108769, 2021 02 23.
Article
em En
| MEDLINE
| ID: mdl-33626351
ABSTRACT
Chromatin dysregulation has emerged as an important mechanism of oncogenesis. To develop targeted treatments, it is important to understand the transcriptomic consequences of mutations in chromatin modifier genes. Recently, mutations in the histone methyltransferase gene nuclear receptor binding SET domain protein 1 (NSD1) have been identified in a subset of common and deadly head and neck squamous cell carcinomas (HNSCCs). Here, we use genome-wide approaches and genome editing to dissect the downstream effects of loss of NSD1 in HNSCC. We demonstrate that NSD1 mutations are responsible for loss of intergenic H3K36me2 domains, followed by loss of DNA methylation and gain of H3K27me3 in the affected genomic regions. In addition, those regions are enriched in cis-regulatory elements, and subsequent loss of H3K27ac correlates with reduced expression of their target genes. Our analysis identifies genes and pathways affected by the loss of NSD1 and paves the way to further understanding the interplay among chromatin modifications in cancer.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cromatina
/
Histona-Lisina N-Metiltransferase
/
Metilação de DNA
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Montagem e Desmontagem da Cromatina
/
Epigênese Genética
/
Carcinoma de Células Escamosas de Cabeça e Pescoço
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Neoplasias de Cabeça e Pescoço
/
Mutação
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Cell Rep
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Canadá