Early B-cell factor regulates the expression of Hemokinin-1 in the olfactory epithelium and differentiating B lymphocytes.
Hemokinin-1, encoded by the TAC4 gene, is a tachykinin most closely related to substance P. Previous studies have shown that TAC4 distinguishes itself from other tachykinins by its predominantly non-neuronal expression profile, particularly in cells of the immune system. Here we report for the first time that the highest levels of TAC4 expression are found in the olfactory epithelium. Furthermore, we identify olfactory neuron-specific transcription factor (Olf-1), also known as early B-cell factor (EBF), as a novel regulator of TAC4 expression. EBF present in the olfactory epithelium and in B cells binds to two sites in the TAC4 promoter and modulates expression in developing B cells. Our findings suggest a role for TAC4 in cell differentiation, and represent a regulatory bridge between the nervous system and the immune system.
Tran
Anne H
AH
Department of Stem Cell and Developmental Biology, Princess Margaret Hospital, Ontario Cancer Institute, University Health Network, 610 University Ave, Toronto, ON, M5G 2M9, Canada. anne.tran@utoronto.ca
Berger
Alexandra
A
Wu
Gillian E
GE
Kee
Barbara L
BL
Paige
Christopher J
CJ
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D001483:Base Sequence; D015152:Blotting, Northern; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002469:Cell Separation; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009831:Olfactory Mucosa / Q000276:immunology* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011498:Protein Precursors / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015320:Tachykinins / Q000096:biosynthesis* / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014162:Transfection
C489921:Ebf1 protein, mouse; D011498:Protein Precursors; C423233:Tac4 protein, mouse; D015320:Tachykinins; D015534:Trans-Activators