Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Más filtros

Banco de datos
Tipo del documento
Intervalo de año de publicación
1.
Sci Adv ; 8(36): eabm2427, 2022 09 09.
Artículo en Inglés | MEDLINE | ID: mdl-36070377

RESUMEN

TET (ten-eleven translocation) enzymes catalyze the oxidation of 5-methylcytosine bases in DNA, thus driving active and passive DNA demethylation. Here, we report that the catalytic domain of mammalian TET enzymes favor CGs embedded within basic helix-loop-helix and basic leucine zipper domain transcription factor-binding sites, with up to 250-fold preference in vitro. Crystal structures and molecular dynamics calculations show that sequence preference is caused by intrasubstrate interactions and CG flanking sequence indirectly affecting enzyme conformation. TET sequence preferences are physiologically relevant as they explain the rates of DNA demethylation in TET-rescue experiments in culture and in vivo within the zygote and germ line. Most and least favorable TET motifs represent DNA sites that are bound by methylation-sensitive immediate-early transcription factors and octamer-binding transcription factor 4 (OCT4), respectively, illuminating TET function in transcriptional responses and pluripotency support.


Asunto(s)
5-Metilcitosina , Dioxigenasas , 5-Metilcitosina/metabolismo , Animales , Dominio Catalítico , Fenómenos Fisiológicos Celulares , ADN , Dioxigenasas/genética , Dioxigenasas/metabolismo , Mamíferos/genética
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA