|
Status |
Public on Nov 04, 2012 |
Title |
Histone acetylation regulates intracellular pH |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing Genome binding/occupancy profiling by high throughput sequencing
|
Summary |
Differences in global levels of histone acetylation occur in normal and cancer cells, although the reason cells regulate these levels has remained unclear. Here we demonstrate a role for histone acetylation in regulating intracellular pH (pHi). As pHi decreases, histones are globally deacetylated by histone deacetylases (HDACs) and the released acetate anions are co-exported with protons out of the cell by monocarboxylate transporters (MCTs), preventing further reductions in pHi. Conversely, global histone acetylation increases at more alkaline pHi, such as when resting cells are induced to proliferate. Inhibition of HDACs or MCTs decreases acetate export and lowers pHi, particularly compromising pHi maintenance in acidic environments. Global deacetylation at low pH is reflected at a genomic level by decreased abundance and extensive redistribution of acetylation at promoters and intergenic regions. Thus acetylation of chromatin functions as a rheostat to regulate pHi with important implications for therapeutic use of HDAC inhibitors.
|
|
|
Overall design |
To investigate the redistribution of H4K16ac throughout the genome upon treatment at pH 6.5
|
|
|
Contributor(s) |
McBrian MA |
Citation(s) |
23201122 |
|
Submission date |
Aug 14, 2012 |
Last update date |
May 15, 2019 |
Contact name |
Siavash K Kurdistani |
E-mail(s) |
Skurdistani@mednet.ucla.edu
|
Organization name |
UCLA
|
Department |
Biological Chemistry
|
Lab |
Kurdistani
|
Street address |
615 Charles E Young Dr South
|
City |
Los Angeles |
State/province |
CA |
ZIP/Postal code |
90095 |
Country |
USA |
|
|
Platforms (1) |
GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
|
Samples (6)
|
|
Relations |
BioProject |
PRJNA172856 |
SRA |
SRP014844 |