Complex pattern of immunoglobulin mu gene expression in normal and transgenic mice: nonoverlapping regulatory sequences govern distinct tissue specificities.
Analysis of normal mice and transgenic mice carrying a rearranged immunoglobulin mu gene revealed a more complex tissue-specific pattern of mu gene expression than anticipated from previous observations. Expression of the endogenous mu locus and the mu transgene was detected both in lymphoid tissues and in skeletal muscle. Analysis of the expression pattern of mu transgenes containing intragenic deletions or point mutations in binding sites for Oct transcription factors (OCTA sites) indicated that distinct regulatory sequences control lymphoid- and muscle-specific mu gene expression. Consistent with previous transfection experiments, mu gene expression in lymphoid tissues is dependent on the intragenic enhancer and the OCTA site in the promoter. However, neither of these regulatory sequences is required for mu gene expression in skeletal muscle that is governed by a muscle-specific control region located 3' of the enhancer. An "off-state" of the mu transgene was observed only in liver and embryonal fibroblasts, whereas enhancer-dependent mu transgene expression was detected at low levels in other nonlymphoid tissues. From these data we suggest a model for the regulation of tissue-specific mu gene expression in which a "ubiquitous" competence for basal transcription is up-regulated in lymphoid and muscle tissues by distinct cell type-specific regulatory sequences and down-regulated in liver and fibroblastic cells by putative negative sequence elements.
Jenuwein
T
T
Howard Hughes Medical Institute, University of California, San Francisco 94143.
Grosschedl
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R
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D007148:Immunoglobulin mu-Chains / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009132:Muscles / Q000378:metabolism; D009928:Organ Specificity / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid; D013154:Spleen / Q000378:metabolism; D013950:Thymus Gland / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D007148:Immunoglobulin mu-Chains; D014157:Transcription Factors; D004247:DNA