Cis-regulatory architecture of human ESC-derived hypothalamic neuron differentiation aids in variant-to-gene mapping of relevant complex traits.
Nat Commun
; 12(1): 6749, 2021 11 19.
Article
en En
| MEDLINE
| ID: mdl-34799566
ABSTRACT
The hypothalamus regulates metabolic homeostasis by influencing behavior and endocrine systems. Given its role governing key traits, such as body weight and reproductive timing, understanding the genetic regulation of hypothalamic development and function could yield insights into disease pathogenesis. However, given its inaccessibility, studying human hypothalamic gene regulation has proven challenging. To address this gap, we generate a high-resolution chromatin architecture atlas of an established embryonic stem cell derived hypothalamic-like neuron model across three stages of in vitro differentiation. We profile accessible chromatin and identify physical contacts between gene promoters and putative cis-regulatory elements to characterize global regulatory landscape changes during hypothalamic differentiation. Next, we integrate these data with GWAS loci for various complex traits, identifying multiple candidate effector genes. Our results reveal common target genes for these traits, potentially affecting core developmental pathways. Our atlas will enable future efforts to determine hypothalamic mechanisms influencing disease susceptibility.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Regulación del Desarrollo de la Expresión Génica
/
Redes Reguladoras de Genes
/
Células Madre Embrionarias Humanas
/
Hipotálamo
/
Neuronas
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Nat Commun
Asunto de la revista:
BIOLOGIA
/
CIENCIA
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos