Nature 319, 154 - 158 (09 January 1986); doi:10.1038/319154a0

A nuclear factor that binds to a conserved sequence motif in transcriptional control elements of immunoglobulin genes

Harinder Singh^*, Ranjan Sen^†, David Baltimore^*† & Phillip A. Sharp^*

^*Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
^†Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA

Trans-acting factors that mediate B-cell specific transcription of immunoglobulin genes have been postulated based on an analysis of the expression of exogenously introduced immunoglobulin gene recombinants in lymphoid and non-lymphoid cells. Two B-cell-specific, cis-acting transcriptional regulatory elements have been identified. One element is located in the intron between the variable (V) and constant (C) regions of both heavy and light-chain genes and acts as a transcriptional enhancer¹⁻⁶. The second element is found upstream of both heavy and light-chain gene promoters. This element directs lymphoid-specific transcription even in the presence of viral enhancers⁷⁻¹⁰. We have sought nuclear factors that might bind specifically to these two regulatory elements by application of a modified gel electrophoresis DNA binding assay¹¹⁻¹³. We report here the identification of a human B-cell nuclear factor (IgNF-A) that binds to DNA sequences in the upstream regions of both the mouse heavy and light-chain gene promoters and also to the mouse heavy-chain gene enhancer. This sequence-specific binding is probably mediated by a highly conserved sequence motif, ATTTGCAT, present in all three transcriptional elements. Interestingly, a factor showing similar binding specificity to IgNF-A is also present in human HeLa cells.

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