title: 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.
authors.affiliation: Department of Biochemistry, Developmental Genetics Focus Group, Center of Excellence in Bioinformatics and Life Sciences, State University of New York at Buffalo, Buffalo, New York, USA.
authors.forename: Shinu
authors.initials: S
authors.lastname: John
authors.forename: Lisa
authors.initials: L
authors.lastname: Russell
authors.forename: Shu Shien
authors.initials: SS
authors.lastname: Chin
authors.forename: Wei
authors.initials: W
authors.lastname: Luo
authors.forename: Robert
authors.initials: R
authors.lastname: Oshima
authors.forename: Lee Ann
authors.initials: LA
authors.lastname: Garrett-Sinha
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000921:Antibody-Producing Cells / Q000187:drug effects / Q000378:metabolism*; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D015153:Blotting, Western; D019556:COS Cells; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D015870:Gene Expression; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009154:Mutation; D059372:Nucleotide Motifs / Q000235:genetics; D051757:PAX5 Transcription Factor / Q000235:genetics / Q000378:metabolism; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011485:Protein Binding; D050784:Proto-Oncogene Protein c-ets-1 / Q000235:genetics / Q000378:metabolism*; D050787:Proto-Oncogene Protein c-ets-2 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: C494042:Ets1 protein, mouse; C494070:Ets2 protein, mouse; D008070:Lipopolysaccharides; D051757:PAX5 Transcription Factor; C497282:Pax5 protein, mouse; C513258:Prdm1 protein, mouse; D050784:Proto-Oncogene Protein c-ets-1; D050787:Proto-Oncogene Protein c-ets-2; D014157:Transcription Factors; D000074462:Positive Regulatory Domain I-Binding Factor 1