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| Status |
Public on Jul 30, 2011 |
| Title |
ChIP-chip from ex-vivo differentiated erythroblasts derived from human primary CD34+ cells |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by genome tiling array
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| 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: Antibody ChIP-chip, Human Primary Erythroblasts
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| Overall design |
Genomic targets of Transcription factor ZBP-89 and Histone 3 acetylation signature were identified by ChIP-chip in human primary cells.
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| Contributor(s) |
Woo AJ, Kim J, Xu J, Huang H, Cantor AB |
| Citation(s) |
21828133 |
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| Submission date |
Jul 29, 2011 |
| Last update date |
Mar 23, 2012 |
| Contact name |
Andrew Jonghan Woo |
| E-mail(s) |
andrew.woo@childrens.harvard.edu
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| Phone |
6179192028
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| Fax |
6177300222
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| Organization name |
Children's Hospital Boston / Harvard Medical School
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| Department |
Hematology / Oncology
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| Lab |
Alan B Cantor Lab
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| Street address |
1 Blackfan Circle, Karp Res Bldg
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| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02115 |
| Country |
USA |
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| Platforms (1) |
| GPL6129 |
GeneChip ENCODEver2.0R Array - NCBI build 36 |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA144909 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE31036_RAW.tar |
238.9 Mb |
(http)(custom) |
TAR (of BAR, BED, CEL) |
| Processed data provided as supplementary file |
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