| First Author | Wang D | Year | 2010 |
| Journal | J Immunol | Volume | 185 |
| Issue | 7 | Pages | 4109-17 |
| PubMed ID | 20826759 | Mgi Jnum | J:164282 |
| Mgi Id | MGI:4831053 | Doi | 10.4049/jimmunol.0901783 |
| Citation | Wang D, et al. (2010) Context-dependent regulation of hematopoietic lineage choice by HEBAlt. J Immunol 185(7):4109-17 |
| abstractText | Hematopoietic development is controlled by combinatorial interactions between E-protein transcription factors and other lineage regulators that operate in the context of gene-regulatory networks. The E-proteins HEB and E2A are critical for T cell and B cell development, but the mechanisms by which their activities are directed to different genes in each lineage are unclear. We found that a short form of HEB, HEBAlt, acts downstream of Delta-like (DL)-Notch signaling to promote T cell development. In this paper, we show that forced expression of HEBAlt in mouse hematopoietic progenitors inhibited B cell development, but it allowed them to adopt a myeloid fate. HEBAlt interfered with the activity of E2A homodimers and with the expression of the transcription factor Pax5, both of which are critical for B cell development. However, when combined with DL-Notch signaling, HEBAlt enhanced the generation of T cell progenitors at the expense of myeloid cells. The longer form of HEB, HEBCan, also inhibited E47 activity and Pax5 expression, but it did not collaborate with DL-Notch signaling to suppress myeloid potential. Therefore, HEBAlt can suppress B cell or myeloid potential in a context-specific manner, which suggests a role for this factor in maintaining T lineage priming prior to commitment. |
