|
| Status |
Public on Aug 02, 2011 |
| Title |
Expression analysis of ZBP-89 deficient human primary erythroid progenitors |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
The molecular mechanisms underlying erythroid-specific gene regulation remain incompletely understood. Closely spaced binding sites for GATA, NF-E2/maf and CACCC interacting transcription factors play functionally important roles in globin and other erythroid-specific gene expression. We and others recently identified the CACCC-binding transcription factor ZBP-89 as a novel GATA-1 and NF-E2/mafK interacting partner. Here, we examined the role of ZBP-89 in human globin gene regulation and erythroid maturation using a primary CD34+ cell ex vivo differentiation system. We show that ZBP-89 protein levels rise dramatically during human erythroid differentiation, and that ZBP-89 occupies key cis-regulatory elements within the globin and other erythroid gene loci. ZBP-89 binding correlates strongly with RNA Pol II occupancy, active histone marks, and high-level gene expression. ZBP-89 physically associates with the histone acetyltransferases (HATs) p300 and Gcn5/Trrap, and occupies common sites with Gcn5 within the human globin loci. Lentiviral shRNA knockdown of ZBP-89 results in reduced Gcn5 occupancy, decreased acetylated histone 3 levels, lower globin and erythroid-specific gene expression, and impaired erythroid maturation. Addition of the HDAC inhibitor valproic acid partially reverses the reduced globin gene expression. These findings reveal an activating role for ZBP-89 in human globin gene regulation and erythroid differentiation.
Keywords: Human primary erythroid progenitors
|
| |
|
| Overall design |
Expression data of human erythroid progenitors transduced with lentivirus expressing short hairpins against ZBP-89 and control empty vector
|
| |
|
| Contributor(s) |
Woo AJ, Kim J, Xu J, Huang H, Cantor AB |
| Citation(s) |
21828133 |
| Submission date |
Aug 01, 2011 |
| Last update date |
Dec 06, 2018 |
| Contact name |
Andrew Jonghan Woo |
| E-mail(s) |
andrew.woo@childrens.harvard.edu
|
| Phone |
6179192028
|
| Fax |
6177300222
|
| Organization name |
Children's Hospital Boston / Harvard Medical School
|
| Department |
Hematology / Oncology
|
| Lab |
Alan B Cantor Lab
|
| Street address |
1 Blackfan Circle, Karp Res Bldg
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02115 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL571 |
[HG-U133A_2] Affymetrix Human Genome U133A 2.0 Array |
|
| Samples (4)
|
|
| Relations |
| BioProject |
PRJNA144709 |
Less...
More...