Hormone-control regions mediate steroid receptor-dependent genome organization.
Genome Res
; 29(1): 29-39, 2019 01.
Article
em En
| MEDLINE
| ID: mdl-30552103
ABSTRACT
In breast cancer cells, some topologically associating domains (TADs) behave as hormonal gene regulation units, within which gene transcription is coordinately regulated in response to steroid hormones. Here we further describe that responsive TADs contain 20- to 100-kb-long clusters of intermingled estrogen receptor (ESR1) and progesterone receptor (PGR) binding sites, hereafter called hormone-control regions (HCRs). In T47D cells, we identified more than 200 HCRs, which are frequently bound by unliganded ESR1 and PGR. These HCRs establish steady long-distance inter-TAD interactions between them and organize characteristic looping structures with promoters in their TADs even in the absence of hormones in ESR1+-PGR+ cells. This organization is dependent on the expression of the receptors and is further dynamically modulated in response to steroid hormones. HCRs function as platforms that integrate different signals, resulting in some cases in opposite transcriptional responses to estrogens or progestins. Altogether, these results suggest that steroid hormone receptors act not only as hormone-regulated sequence-specific transcription factors but also as local and global genome organizers.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Progesterona
/
Transdução de Sinais
/
Receptores de Progesterona
/
Regulação da Expressão Gênica
/
Elementos de Resposta
/
Receptor alfa de Estrogênio
/
Estrogênios
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Genome Res
Assunto da revista:
BIOLOGIA MOLECULAR
/
GENETICA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Espanha