An Epigenomic fingerprint of human cancers by landscape interrogation of super enhancers at the constituent level.
PLoS Comput Biol
; 20(2): e1011873, 2024 Feb.
Article
em En
| MEDLINE
| ID: mdl-38335222
ABSTRACT
Super enhancers (SE), large genomic elements that activate transcription and drive cell identity, have been found with cancer-specific gene regulation in human cancers. Recent studies reported the importance of understanding the cooperation and function of SE internal components, i.e., the constituent enhancers (CE). However, there are no pan-cancer studies to identify cancer-specific SE signatures at the constituent level. Here, by revisiting pan-cancer SE activities with H3K27Ac ChIP-seq datasets, we report fingerprint SE signatures for 28 cancer types in the NCI-60 cell panel. We implement a mixture model to discriminate active CEs from inactive CEs by taking into consideration ChIP-seq variabilities between cancer samples and across CEs. We demonstrate that the model-based estimation of CE states provides improved functional interpretation of SE-associated regulation. We identify cancer-specific CEs by balancing their active prevalence with their capability of encoding cancer type identities. We further demonstrate that cancer-specific CEs have the strongest per-base enhancer activities in independent enhancer sequencing assays, suggesting their importance in understanding critical SE signatures. We summarize fingerprint SEs based on the cancer-specific statuses of their component CEs and build an easy-to-use R package to facilitate the query, exploration, and visualization of fingerprint SEs across cancers.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Super Intensificadores
/
Neoplasias
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
PLoS Comput Biol
/
PloS comput. biol
/
PloS computational biology
Assunto da revista:
BIOLOGIA
/
INFORMATICA MEDICA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos