Alternative titles; symbols
HGNC Approved Gene Symbol: EBF1
Cytogenetic location: 5q33.3 Genomic coordinates (GRCh38): 5:158,695,920-159,099,916 (from NCBI)
Using a novel genetic selection in yeast, Wang and Reed (1993) isolated a cDNA for the rat transcriptional activator Olf1, which binds to the regulatory sequences of several olfactory-specific genes. Expressed exclusively in the olfactory receptor neurons and their precursors, the Olf1 protein contains a new helix-loop-helix motif and functions as an apparent homodimer. They suggested that Olf1 may be the first member of a family of related proteins that may direct cellular differentiation in a variety of neuronal tissues.
Early B-cell factor (EBF) is a tissue-specific and differentiation stage-specific DNA-binding protein that participates in the regulation of the pre-B and B lymphocyte-specific MB1 (112205) gene. Travis et al. (1993) purified the mouse Ebf protein from pre-B cells and found that it is composed of two 62- to 65-kD subunits. Hagman et al. (1993) determined partial amino acid sequences of Ebf and used them to isolate mouse pre-B-cell cDNAs encoding Ebf. The predicted 591-amino acid protein has 2 functional domains: an N-terminal cysteine-rich region essential for DNA binding, and a C-terminal dimerization region containing two 15-amino acid repeats with similarity to the dimerization domains of basic helix-loop-helix (bHLH) proteins. The calculated molecular mass of the encoded Ebf protein is 64.4 kD. The authors found that recombinant Ebf binds to DNA as a homodimer, forms complexes with the Mb1 promoter, and is a strong activator of transcription. Northern blot analysis detected multiple Ebf transcripts in pre-B- and early B-cell lines but not in other hematopoietic cells. S1 nuclease protection analysis of adult mouse RNAs showed high levels of Ebf expression in lymph node, spleen, and adipose tissues and low levels in several nonlymphoid tissues.
Mice lacking Ebf are unable develop B lymphoid cells (Lin and Grosschedl, 1995). Using 5-prime RACE and primer extension analysis, Smith et al. (2002) identified a promoter element able to stimulate transcription and cloned an EBF variant. The promoter region is able to stimulate transcription in B, but not pre-T, lymphoid cell lines and also to interact with E47 (TCF3; 147141) and Ebf itself, suggesting that the EBF gene is a direct target for E47, and that EBF expression is controlled by autoregulation.
By Southern blot analysis of somatic cell hybrid DNAs using a murine Ebf cDNA as a probe, and by fluorescence in situ hybridization using human genomic cosmids, Milatovich et al. (1994) mapped the human EBF gene to 5q34. They mapped the mouse Ebf gene to proximal chromosome 11 by Southern blot analysis of somatic cell hybrid DNAs and by analysis of recombinant inbred strains.
Gimelbrant et al. (2007) used a genomewide approach to assess allele-specific transcription of about 4,000 human genes in clonal cell lines and found that more than 300 were subject to random monoallelic expression. One of these genes was EBF. Gimelbrant et al. (2007) concluded that an unexpectedly widespread monoallelic expression suggested a mechanism that generates diversity in individual cells and their clonal descendants.
Using gain- and loss-of-function approaches to uncover the transcriptional mechanism underpinning mouse Ebf1-mediated suppression of T-cell development, Banerjee et al. (2013) showed that Ebf1 promoted B-cell lineage commitment by directly repressing expression of Gata3 (131320), which is required by the T-cell lineage. Lymphoid progenitor cells deficient in Ebf1 exhibited increased T-cell lineage potential and elevated expression of Gata3 transcript. Enforced expression of Ebf1 inhibited T-cell differentiation and caused rapid loss of Gata3 mRNA. A synthetic zinc-finger polypeptide, 6ZFP, perturbed binding of Ebf1 to the Gata3 regulatory region and restored Gata3 expression, allowing T-cell differentiation while blocking B-cell differentiation. Banerjee et al. (2013) concluded that these data identify the mechanisms involved in the transcriptional circuit critical for B-cell lineage commitment.
In a genomewide analysis of leukemic cells from 242 pediatric acute lymphocytic leukemia (ALL; 613065) patients using high resolution, single-nucleotide polymorphism (SNP) arrays and genomic DNA sequencing, Mullighan et al. (2007) identified mutations in genes encoding principal regulators of B-lymphocyte development and differentiation in 40% of B-progenitor ALL cases. Deletions were detected in EBF1, IKZF1 (603023), IKZF3 (606221), TCF3 (147141), and LEF1 (153245). The PAX5 (167414) gene was the most frequent target of somatic mutation, being altered in 31.7% of cases.
Stolfi et al. (2010) found that heart progenitor cells of the simple chordate Ciona intestinalis generated precursors of the atrial siphon muscles. These precursors expressed Islet (ISL1; 600366) and Tbx1 (602054)/Tbx10 (604648), evocative of the splanchnic mesoderm that produces the lower jaw muscles and second heart field of vertebrates. Stolfi et al. (2010) presented evidence identifying the transcription factor Coe as a critical determinant of atrial siphon muscle fate. They proposed that the last common ancestor of tunicates and vertebrates possessed multipotent cardiopharyngeal muscle precursors, and that their reallocation might have contributed to the emergence of the second heart field.
The mammalian olfactory system has the remarkable ability to detect odorants with high sensitivity and specificity. The initial events in the olfactory signal transduction pathway occur in the specialized cilia of the sensory neurons. Unlike other neurons, the olfactory sensory cells are continually replaced throughout adult life. Cells within the olfactory epithelium follow an orderly developmental program resulting in the high level of expression of gene products essential for odorant signal transduction. The mature neurons express several olfactory-specific genes, some of which appear to mediate the odorant signal transduction cascade. Evidence supporting the involvement of a G protein-coupled receptor pathway in odorant signal transduction was provided by the isolation of olfactory-specific components that correspond to each step in the pathway, e.g., G-alpha-olf (139312). Additional olfactory neuron-specific genes have been identified. The establishment of the mature olfactory neuronal phenotype probably results from the coordinated expression of olfactory-specific genes. In the investigation of these genes, Wang and Reed (1993) found that each contains at least 1 binding site for the DNA-binding protein Olf1. The binding of an olfactory-specific factor, Olf1, was first described in the olfactory marker protein gene (OMP; 164340). Olf1 activity was detectable in nuclear extracts from nasal epithelium and absent from nuclear extracts of a variety of other tissues.
Banerjee, A., Northrup, D., Boukarabila, H., Jacobsen, S. E. W., Allman, D. Transcriptional repression of Gata3 is essential for early B cell commitment. Immunity 38: 930-942, 2013. [PubMed: 23684985] [Full Text: https://doi.org/10.1016/j.immuni.2013.01.014]
Gimelbrant, A., Hutchinson, J. N., Thompson, B. R., Chess, A. Widespread monoallelic expression on human autosomes. Science 318: 1136-1140, 2007. [PubMed: 18006746] [Full Text: https://doi.org/10.1126/science.1148910]
Hagman, J., Belanger, C., Travis, A., Turck, C. W., Grosschedl, R. Cloning and functional characterization of early B-cell factor, a regulator of lymphocyte-specific gene expression. Genes Dev. 7: 760-773, 1993. [PubMed: 8491377] [Full Text: https://doi.org/10.1101/gad.7.5.760]
Lin, H., Grosschedl, R. Failure of B-cell differentiation in mice lacking the transcription factor EBF. Nature 376: 263-267, 1995. [PubMed: 7542362] [Full Text: https://doi.org/10.1038/376263a0]
Milatovich, A., Qiu, R.-G., Grosschedl, R., Francke, U. Gene for a tissue-specific transcriptional activator (EBF or Olf-1), expressed in early B lymphocytes, adipocytes, and olfactory neurons, is located on human chromosome 5, band q34, and proximal mouse chromosome 11. Mammalian Genome 5: 211-215, 1994. [PubMed: 8012110] [Full Text: https://doi.org/10.1007/BF00360547]
Mullighan, C. G., Goorha, S., Radtke, I., Miller, C. B., Coustan-Smith, E., Dalton, J. D., Girtman, K., Mathew, S., Ma, J., Pounds, S. B., Su, X., Pui, C.-H., Relling, M. V., Evans, W. E., Shurtleff, S. A., Downing, J. R. Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia. Nature 446: 758-764, 2007. [PubMed: 17344859] [Full Text: https://doi.org/10.1038/nature05690]
Smith, E. M., Gisler, R., Sigvardsson, M. Cloning and characterization of a promoter flanking the early B cell factor (EBF) gene indicates roles for E-proteins and autoregulation in the control of EBF expression. J. Immun. 169: 261-270, 2002. [PubMed: 12077253] [Full Text: https://doi.org/10.4049/jimmunol.169.1.261]
Stolfi, A., Gainous, T. B., Young, J. J., Mori, A., Levine, M., Christiaen, L. Early chordate origins of the vertebrate second heart field. Science 329: 565-568, 2010. [PubMed: 20671188] [Full Text: https://doi.org/10.1126/science.1190181]
Travis, A., Hagman, J., Hwang, L., Grosschedl, R. Purification of early-B-cell factor and characterization of its DNA-binding specificity. Molec. Cell. Biol. 13: 3392-3400, 1993. [PubMed: 8497258] [Full Text: https://doi.org/10.1128/mcb.13.6.3392-3400.1993]
Wang, M. M., Reed, R. R. Molecular cloning of the olfactory neuronal transcription factor Olf-1 by genetic selection in yeast. Nature 364: 121-126, 1993. [PubMed: 8321284] [Full Text: https://doi.org/10.1038/364121a0]