Transcription Factor Ets1, but Not the Closely Related Factor Ets2, Inhibits Antibody-Secreting Cell Differentiation

Abstract

B cell differentiation into antibody-secreting cells (ASCs) is a tightly regulated process under the control of multiple transcription factors. One such transcription factor, Ets1, blocks the transition of B cells to ASCs via two separate activities: (i) stimulating the expression of target genes that promote B cell identity and (ii) interfering with the functional activity of the transcription factor Blimp1. Ets1 is a member of a multigene family, several members of which are expressed within the B cell lineage, including the closely related protein Ets2. In this report, we demonstrate that Ets1, but not Ets2, can block ASC formation despite the fact that Ets1 and Ets2 bind to apparently identical DNA sequence motifs and are thought to regulate overlapping sets of target genes. The DNA binding domain of Ets1 is required, but not sufficient by itself, to block ASC formation. In addition, less conserved regions within the N terminus of Ets1 play an important role in inhibiting B cell differentiation. Differences between the N termini of Ets1 and Ets2, rather than differences in the DNA binding domains, determine whether the proteins are capable of blocking ASC formation or not.

SUPPLEMENTAL MATERIAL

Supplemental material for this article may be found at http://dx.doi.org/10.1128/MCB.00612-13.

ACKNOWLEDGMENTS

We thank Satrajit Sinha for helpful comments and Irene Kulik for technical assistance. We also thank Michael Ostrowski for providing antibody to Ets2 used in Western blotting and Michael Buck for advice on chromatin immunoprecipitation experiments.

These studies were supported by research grants from the Lupus Research Institute and the National Institutes of Health (AI085127).