The murine lymphotoxin gene promoter. Characterization and negative regulation.
Murine lymphotoxin (LT; TNF-beta) gene upstream regulatory elements were identified by linking fragments of 5' DNA to the chloramphenicol acetyl transferase gene. Fragment LT1 (-293 to +77 in relation to the proximal cap site) exhibited promoter activity which drove CAT expression in transfected murine fibroblasts and T lymphomas. Primer extension analysis of endogenous LT message confirmed that LT1 contained the necessary elements required for promoter function. Promoter activity was not observed when LT2 (-662 to +77), LT3 (-1186 to +77), or LT3 delta AX (-1186 to +77 (delta-662/-269)) were ligated to the chloramphenicol acetyl transferase gene and transfected into fibroblasts or T lymphomas. At least one upstream repressor element is postulated to account for this promoter inhibition. In contrast to the results obtained with fibroblast and T cell transfectants, LT1 was inactive in the B cell transfectants A20 and P3X63. This suggests that some B cells express a repressor factor that inhibits the LT promoter and/or they lack the necessary positive regulatory factors.
Fashena
S J
SJ
Department of Biology, Yale University, New Haven, CT 06510.
Tang
W L
WL
Sarr
T
T
Ruddle
N H
NH
D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D005347:Fibroblasts / Q000502:physiology; D005786:Gene Expression Regulation; D008223:Lymphoma / Q000235:genetics; D008233:Lymphotoxin-alpha / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid; D015183:Restriction Mapping; D013601:T-Lymphocytes / Q000502:physiology
D008233:Lymphotoxin-alpha; D012333:RNA, Messenger