ETS-core binding factor: a common composite motif in antigen receptor gene enhancers.
A tripartite domain of the murine immunoglobulin mu heavy-chain enhancer contains the muA and muB elements that bind ETS proteins and the muE3 element that binds leucine zipper-containing basic helix-loop-helix (bHLH-zip) factors. Analysis of the corresponding region of the human mu enhancer revealed high conservation of the muA and muB motifs but a striking absence of the muE3 element. Instead of bHLH-zip proteins, we found that the human enhancer bound core binding factor (CBF) between the muA and mu elements; CBF binding was shown to be a common feature of both murine and human enhancers. Furthermore, mutant enhancers that bound prototypic bHLH-zip proteins but not CBF did not activate transcription in B cells, and conversely, CBF transactivated the murine enhancer in nonlymphoid cells. Taking these data together with the earlier analysis of T-cell-specific enhancers, we propose that ETS-CBF is a common composite element in the regulation of antigen receptor genes. In addition, these studies identify the first B-cell target of CBF, a protein that has been implicated in the development of childhood pre-B-cell leukemias.
Erman
B
B
Rosenstiel Research Center and Department of Biology, Brandeis University, Waltham, Massachusetts 02254, USA.
Cortes
M
M
Nikolajczyk
B S
BS
Speck
N A
NA
Sen
R
R
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D001483:Base Sequence; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D002457:Cell Extracts; D002467:Cell Nucleus / Q000378:metabolism; D050660:Core Binding Factors; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D006367:HeLa Cells; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007148:Immunoglobulin mu-Chains / Q000235:genetics*; D050835:Interferon Regulatory Factors; D008214:Lymphocytes; D051379:Mice; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D050783:Proto-Oncogene Proteins c-ets; D011946:Receptors, Antigen / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D051720:Upstream Stimulatory Factors; D000099218:Interferon Regulatory Factor-4
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D002457:Cell Extracts; D050660:Core Binding Factors; D004268:DNA-Binding Proteins; D007143:Immunoglobulin Heavy Chains; D007148:Immunoglobulin mu-Chains; D050835:Interferon Regulatory Factors; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D011946:Receptors, Antigen; D015534:Trans-Activators; D014157:Transcription Factors; D051720:Upstream Stimulatory Factors; D000099218:Interferon Regulatory Factor-4; C069203:TFE3 protein, human