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
in 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Transcription, Genetic
/
Chromatin
/
Chromosomal Proteins, Non-Histone
/
Sirtuins
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Heme Oxygenase-1
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NF-E2-Related Factor 2
/
Membrane Proteins
Limits:
Animals
Language:
En
Journal:
Nucleic Acids Res
Year:
2019
Document type:
Article
Affiliation country:
United States