Abstract
The human AP-endonuclease (APE1/Ref-1), a multifunctional protein central to repairing abasic sites and single-strand breaks in DNA, also plays a role in transcriptional regulation. Besides activating some transcription factors, APE1 is directly involved in Ca2+-dependent downregulation of parathyroid hormone (PTH) expression by binding to negative calcium response elements (nCaREs) present in the PTH promoter. Here we show that APE1 is acetylated both in vivo and in vitro by the transcriptional co-activator p300 which is activated by Ca2+. Acetylation at Lys6 or Lys7 enhances binding of APE1 to nCaRE. APE1 stably interacts with class I histone deacetylases (HDACs) in vivo. An increase in extracellular calcium enhances the level of acetylated APE1 which acts as a repressor for the PTH promoter. Moreover, chromatin immunoprecipitation (ChIP) assay revealed that acetylation of APE1 enhanced binding of the APE1-HDACs complex to the PTH promoter. These results indicate that acetylation of APE1 plays an important role in this key repair protein's action in transcriptional regulation.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 6299-6309 |
| Number of pages | 11 |
| Journal | EMBO Journal |
| Volume | 22 |
| Issue number | 23 |
| DOIs | |
| State | Published - Dec 1 2003 |
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Keywords
- Acetylation
- AP-endonuclease
- Chromatin immunoprecipitation
- Histone deacetylase
- nCaRE
- p300
ASJC Scopus subject areas
- Genetics
- Cell Biology
Cite this
Role of acetylated human AP-endonuclease (APE1/Ref-1) in regulation of the parathyroid hormone gene. / Bhakat, Kishor K.; Izumi, Tadahide; Yang, Suk Hoon; Hazra, Tapas; Mitra, Sankar.
In: EMBO Journal, Vol. 22, No. 23, 01.12.2003, p. 6299-6309.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Role of acetylated human AP-endonuclease (APE1/Ref-1) in regulation of the parathyroid hormone gene
AU - Bhakat, Kishor K.
AU - Izumi, Tadahide
AU - Yang, Suk Hoon
AU - Hazra, Tapas
AU - Mitra, Sankar
PY - 2003/12/1
Y1 - 2003/12/1
N2 - The human AP-endonuclease (APE1/Ref-1), a multifunctional protein central to repairing abasic sites and single-strand breaks in DNA, also plays a role in transcriptional regulation. Besides activating some transcription factors, APE1 is directly involved in Ca2+-dependent downregulation of parathyroid hormone (PTH) expression by binding to negative calcium response elements (nCaREs) present in the PTH promoter. Here we show that APE1 is acetylated both in vivo and in vitro by the transcriptional co-activator p300 which is activated by Ca2+. Acetylation at Lys6 or Lys7 enhances binding of APE1 to nCaRE. APE1 stably interacts with class I histone deacetylases (HDACs) in vivo. An increase in extracellular calcium enhances the level of acetylated APE1 which acts as a repressor for the PTH promoter. Moreover, chromatin immunoprecipitation (ChIP) assay revealed that acetylation of APE1 enhanced binding of the APE1-HDACs complex to the PTH promoter. These results indicate that acetylation of APE1 plays an important role in this key repair protein's action in transcriptional regulation.
AB - The human AP-endonuclease (APE1/Ref-1), a multifunctional protein central to repairing abasic sites and single-strand breaks in DNA, also plays a role in transcriptional regulation. Besides activating some transcription factors, APE1 is directly involved in Ca2+-dependent downregulation of parathyroid hormone (PTH) expression by binding to negative calcium response elements (nCaREs) present in the PTH promoter. Here we show that APE1 is acetylated both in vivo and in vitro by the transcriptional co-activator p300 which is activated by Ca2+. Acetylation at Lys6 or Lys7 enhances binding of APE1 to nCaRE. APE1 stably interacts with class I histone deacetylases (HDACs) in vivo. An increase in extracellular calcium enhances the level of acetylated APE1 which acts as a repressor for the PTH promoter. Moreover, chromatin immunoprecipitation (ChIP) assay revealed that acetylation of APE1 enhanced binding of the APE1-HDACs complex to the PTH promoter. These results indicate that acetylation of APE1 plays an important role in this key repair protein's action in transcriptional regulation.
KW - Acetylation
KW - AP-endonuclease
KW - Chromatin immunoprecipitation
KW - Histone deacetylase
KW - nCaRE
KW - p300
UR - http://www.scopus.com/inward/record.url?scp=0347504848&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0347504848&partnerID=8YFLogxK
U2 - 10.1093/emboj/cdg595
DO - 10.1093/emboj/cdg595
M3 - Article
VL - 22
SP - 6299
EP - 6309
JO - EMBO Journal
JF - EMBO Journal
SN - 0261-4189
IS - 23
ER -