SIRT6 promotes transcription of a subset of NRF2 targets by mono-ADP-ribosylating BAF170.
Nucleic Acids Res
; 47(15): 7914-7928, 2019 09 05.
Article
en En
| MEDLINE
| ID: mdl-31216030
ABSTRACT
SIRT6 is critical for activating transcription of Nuclear factor (erythroid-derived 2)-like 2 (NRF2) responsive genes during oxidative stress. However, while the mechanism of SIRT6-mediated silencing is well understood, the mechanism of SIRT6-mediated transcriptional activation is unknown. Here, we employed SIRT6 separation of function mutants to reveal that SIRT6 mono-ADP-ribosylation activity is required for transcriptional activation. We demonstrate that SIRT6 mono-ADP-ribosylation of BAF170, a subunit of BAF chromatin remodeling complex, is critical for activation of a subset of NRF2 responsive genes upon oxidative stress. We show that SIRT6 recruits BAF170 to enhancer region of the Heme oxygenase-1 locus and promotes recruitment of RNA polymerase II. Furthermore, SIRT6 mediates the formation of the active chromatin 10-kb loop at the HO-1 locus, which is absent in SIRT6 deficient tissue. These results provide a novel mechanism for SIRT6-mediated transcriptional activation, where SIRT6 mono-ADP-ribosylates and recruits chromatin remodeling proteins to mediate the formation of active chromatin loop.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Transcripción Genética
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Cromatina
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Proteínas Cromosómicas no Histona
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Sirtuinas
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Hemo-Oxigenasa 1
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Factor 2 Relacionado con NF-E2
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Proteínas de la Membrana
Límite:
Animals
Idioma:
En
Revista:
Nucleic Acids Res
Año:
2019
Tipo del documento:
Article
País de afiliación:
Estados Unidos