Trim28 Haploinsufficiency Triggers Bi-stable Epigenetic Obesity.
Cell
; 164(3): 353-64, 2016 Jan 28.
Article
en En
| MEDLINE
| ID: mdl-26824653
ABSTRACT
More than one-half billion people are obese, and despite progress in genetic research, much of the heritability of obesity remains enigmatic. Here, we identify a Trim28-dependent network capable of triggering obesity in a non-Mendelian, "on/off" manner. Trim28(+/D9) mutant mice exhibit a bi-modal body-weight distribution, with isogenic animals randomly emerging as either normal or obese and few intermediates. We find that the obese-"on" state is characterized by reduced expression of an imprinted gene network including Nnat, Peg3, Cdkn1c, and Plagl1 and that independent targeting of these alleles recapitulates the stochastic bi-stable disease phenotype. Adipose tissue transcriptome analyses in children indicate that humans too cluster into distinct sub-populations, stratifying according to Trim28 expression, transcriptome organization, and obesity-associated imprinted gene dysregulation. These data provide evidence of discrete polyphenism in mouse and man and thus carry important implications for complex trait genetics, evolution, and medicine.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Proteínas Represoras
/
Delgadez
/
Proteínas Nucleares
/
Epigénesis Genética
/
Haploinsuficiencia
/
Obesidad
Tipo de estudio:
Prognostic_studies
Límite:
Adolescent
/
Animals
/
Child
/
Child, preschool
/
Humans
Idioma:
En
Revista:
Cell
Año:
2016
Tipo del documento:
Article
País de afiliación:
Alemania