HERF1, a Novel Hematopoiesis-Specific RING Finger Protein, Is Required for Terminal Differentiation of Erythroid Cells

Abstract

The AML1/core binding factor β (CBFβ) transcription factor is essential for definitive hematopoiesis; however, the downstream pathways through which it functions remain incompletely defined. Using a differential cloning approach to define components of this pathway, we have identified a novel gene designated HERF1 (for hematopoietic RING finger 1), whose expression during development is dependent on the presence of functional AML1/CBFβ. HERF1 contains a tripartite RING finger–B box–α-helical coiled-coil domain and a C-terminal region homologous to the retproto-oncogene-encoded finger protein. Expression of HERF1during embryogenesis coincides with the appearance of definitive erythropoiesis and in adult mice is restricted to erythroid cells, increasing 30-fold during terminal differentiation. Importantly, inhibition of HERF1 expression blocked terminal erythroid differentiation of the murine erythroleukemia cell line MEL, whereas its overexpression induced erythroid maturation. These results suggest an important role for this protein in erythropoiesis.

ACKNOWLEDGMENTS

We thank Shouli Yang, Noel Lenny, and Zhongling Cai for excellent technical assistance and A. Thomas Look, Gerard Grosveld, Gerard Zambetti, and John Cleveland for helpful discussions and critical reading of the manuscript.

This work was supported by National Institutes of Health (NIH) grant P01 CA71907-03, NIH Cancer Center CORE grant CA-21765, and the American Lebanese Syrian Associated Charities (ALSAC), St. Jude Children’s Research Hospital.