Coordinate transcriptional control of murine endogenous retrovirus and Ig genes during B cell differentiation.
Proliferation and differentiation of B lymphocytes are usually concurrent but independently regulated events. Anti-mu treatment of murine B lymphocytes stimulated with LPS provides a model system in which proliferation and differentiation may be independently studied. This treatment causes enhanced proliferation but with coordinate suppression of transcription of a family of unrelated genes including those for Ig heavy and light chains, J chain, and endogenous murine leukemia virus (MuLV) sequences. We show that in comparison to B lymphocytes stimulated with LPS alone cells stimulated with a combination of anti-mu and LPS exhibit relatively increased amounts of a nuclear binding factor(s), NF mu E1, which interacts with the B (mu E1) site of the IgH enhancer; binding is strongly inhibited by a synthetic probe of the B sequence. A negative regulatory sequence contained within the upstream conserved region (UCR) of the MuLV long terminal repeat (LTR) is identical to the complement of mu E1 in eight of nine bases and inhibits binding of NF mu E1 to the IgH enhancer probe. The mu E1 site is also present 3' to the kappa-light chain gene; binding of this sequence to a repressor protein may coordinately suppress the transcription of mu, kappa, and MuLV genes. Others have reported that the cDNA encoding NF mu E1, also known as mu EBP-B, CF-1, and YY-1, predicts a protein with structural features consistent with variable function as either a transcriptional activator or repressor.
Hummell
D S
DS
Department of Pediatrics, Vanderbilt University, Nashville, TN 37232-2580.
Dooley
J S
JS
Khan
A S
AS
Lawton
A R
AR
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000502:physiology*; D001483:Base Sequence; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D005260:Female; D005786:Gene Expression Regulation; D015967:Gene Expression Regulation, Viral; D005803:Genes, Immunoglobulin; D007148:Immunoglobulin mu-Chains / Q000235:genetics; D009052:Leukemia Virus, Murine / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D007148:Immunoglobulin mu-Chains; D009687:Nuclear Proteins; D012333:RNA, Messenger; D012367:RNA, Viral