Novel Evolutionary-Conserved Role for the ADNP Protein Family that is Important for Erythropoiesis
- Authors
- Dresner, E., Malishkevich, A., Arviv, C., Leibman Barak, S., Alon, S., Ofir, R., Gothilf, Y., and Gozes, I.
- ID
- ZDB-PUB-121019-39
- Date
- 2012
- Source
- The Journal of biological chemistry 287(48): 40173-40185 (Journal)
- Registered Authors
- Gothilf, Yoav
- Keywords
- development, erythrocyte, erythropeisis, hemoglobin, neurodevelopment
- MeSH Terms
-
- Animals
- Cell Line, Tumor
- Erythroid Cells/cytology*
- Erythroid Cells/metabolism
- Erythropoiesis*
- Evolution, Molecular*
- Humans
- Mice
- Molecular Sequence Data
- Multigene Family*
- Nerve Tissue Proteins/genetics*
- Nerve Tissue Proteins/metabolism
- Zebrafish/embryology
- Zebrafish/genetics*
- Zebrafish/metabolism
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism
- PubMed
- 23071114 Full text @ J. Biol. Chem.
Activity-dependent neuroprotective protein (ADNP) and its homologue ADNP2 belong to a homeodomain, zinc-fingers containing protein family. ADNP is essential for mouse embryonic brain formation. ADNP2 is associated with cell survival, but its role in embryogenesis has not been evaluated. Here, we describe the use of the zebrafish model to elucidate the developmental roles of ADNP and ADNP2. While expecting brain defects, we were astonished to discover that the knockdown zebrafish embryos were actually lacking blood and suffered from defective hemoglobin production. Evolutionary-conservation was established using mouse erythroleukemia cells (MEL), a well-studied erythropoiesis model, in which silencing of ADNP or ADNP2 produced similar results as in zebrafish. Exogenous RNA encoding ADNP/ADNP2 rescued the MEL cell undifferentiated state, demonstrating phenotype specificity. Brg1, an ADNP interacting chromatin-remodeling protein involved in erythropoiesis through regulation of the globin locus, was shown here to interact also with ADNP2. Furthermore, chromatin immunoprecipitation revealed recruitment of ADNP, similar Brg1, to the mouse β-globin locus control region (LCR) in MEL cells. This recruitment was apparently diminished upon dimethylsulfoxide (DMSO) induced erythrocyte differentiation compared to the non-differentiated state. Importantly, exogenous RNA encoding ADNP/ADNP2 significantly increased β-globin expression in MEL cells in the absence of any other differentiation factor. Taken together, our results reveal an ancestral role for the ADNP protein family in maturation and differentiation of the erythroid lineage, associated with direct regulation of β-globin expression.