Acetylation of C/EBPε is a prerequisite for terminal neutrophil differentiation
| Autor: | Stephin J. Vervoort, Anita M.A.P. Govers, Paul J. Coffer, Arjan B. Brenkman, Ana Rita Lourenço, Jorg van Loosdregt, Marc Bierings, Rogier van Gent, Veerle Fleskens, Steven J. Ackerman, Cornelieke Pals, Marije Bartels |
|---|---|
| Přispěvatelé: | Gastroenterology & Hepatology |
| Rok vydání: | 2015 |
| Předmět: |
Transcription
Genetic Neutrophils Recombinant Fusion Proteins Cellular differentiation Immunology SUMO protein BETA HL-60 Cells Biology Research Support Biochemistry Sirtuin 1 Neutrophil differentiation Cell Line Tumor Enhancer binding Chlorocebus aethiops Journal Article Animals Humans p300-CBP Transcription Factors Collagenases GRANULE DEFICIENCY MODULATION Non-U.S. Gov't Transcription factor BINDING-PROTEIN-EPSILON Myelopoiesis MYELOID TRANSCRIPTION FACTOR Lysine Research Support Non-U.S. Gov't GRANULOPOIESIS REPRESSION Acetylation Cell Differentiation Cell Biology Hematology GENE Molecular biology Lactoferrin MICE COS Cells CCAAT-Enhancer-Binding Proteins Tertiary granule Ectopic expression STEM-CELLS |
| Zdroj: | Blood, 125(11), 1782. American Society of Hematology Blood, 125(11), 1782-1792. American Society of Hematology |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood-2013-12-543850 |
| Popis: | C/EBPε, a member of the CCAAT/enhancer binding protein (C/EBP) family of transcription factors, is exclusively expressed in myeloid cells and regulates transition from the promyelocytic stage to the myelocytic stage of neutrophil development, being indispensable for secondary and tertiary granule formation. Knowledge concerning the functional role of C/EBPε posttranslational modifications is limited to studies concerning phosphorylation and sumoylation. In the current study, using ectopic expression and ex vivo differentiation of CD34(+) hematopoietic progenitor cells, we demonstrate that C/EBPε is acetylated, which was confirmed by mass spectrometry analysis, identifying 4 acetylated lysines in 3 distinct functional domains. Regulation of C/EBPε acetylation levels by the p300 acetyltransferase and the sirtuin 1 deacetylase controls transcriptional activity, which can at least in part be explained by modulation of DNA binding. During neutrophil development, acetylation of lysines 121 and 198 were found to be crucial for terminal neutrophil differentiation and the expression of neutrophil-specific granule proteins, including lactoferrin and collagenase. Taken together, our data illustrate a critical role for acetylation in the functional regulation of C/EBPε activity during terminal neutrophil development. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|