Open AccessAcetylation of GATA4 on Lysine Residue K313 Promotes Osteoblastic Cells Growth
Author(s) -
Wenjun You,
Lijuan Song,
Kun Wang
Publication year - 2018
Publication title -
cellular physiology and biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.486
H-Index - 87
eISSN - 1421-9778
pISSN - 1015-8987
DOI - 10.1159/000488428
Subject(s) - acetylation , gata4 , hdac4 , chemistry , transfection , microbiology and biotechnology , transcription factor , biology , biochemistry , gene , histone methyltransferase
Background/Aims: GATA4, a protein related to osteoblast differentiation and mineralization, whose acetylation is essential for cardiac defects. Here, we aimed to explore the functional impacts of GATA4 acetylation on osteoporosis (OS). Methods: GATA4 acetylation in hFOB1.19 and 293T cells was detected after exposure of HDAC inhibitors (TSA and SAHA). Co-immunoprecipitation was conducted to determine which HATs and HDACs was involved in the modulation of GATA4 acetylation/deacetylation, and to identify the acetylation site. The transcriptional activity of GATA4 was measured in the presence or absence of cycloheximide. Furthermore, hFOB1.19 cells viability and apoptosis were evaluated after transfection with acetylation-defective mutant of GATA4. Results: As a result, GATA4 acetylation was identified as a pivotal event in hFOB1.19 cells. GATA4 can be acetylated by P300/CBP, and the acetylation site was on lysine residue K313. Besides, the acetylation of GATA4 can be impaired by HDAC1, rather than by HDAC2-5. GATA4 acetylation contributed to the stability and transcription of GATA4. Moreover, GATA4 acetylation activated CCND2 transcription, and mutation of GATA4 on K-313 reduced cell viability and increased a mitochondria-dependent apoptosis in hFOB1.19 cells. Conclusion: Our data suggest that GATA4 exists as an acetylated protein in hFOB1.19 cells. Acetylation regulates the stability and transcription of GATA4, and activates CCND2 transcription, which may explain the growth-promoting functions of GATA4 in hFOB1.19 cells.