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Constitutive and tissue-specific protein factors which bind to transcriptional regulatory elements of Ig genes (promoter and enhancer) are described. The factors were identified and isolated by an improved assay for protein-DNA binding. Genes encoding factors which positively regulate transcription can be isolated and employed to enhance transription of Ig genes. In particular, NF-kB, the gene encoding NF-kB, IkB and the gene encoding IkB and uses therefor.

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Claims

1. A method for inhibiting expression, in a eukaryotic cell, of a gene whose transcription is regulated by NF-KB, the method comprising reducing NF-KB activity in the cell such that expression of said gene is inhibited.

2. A method for selectively inhibiting expression, in a eukaryotic cell, of genes whose transcription is regulated by NF-B, the method comprising reducing NF-B activity in the cell such that expression of said genes is inhibited.

3. A method for reducing the level of expression of a viral gene whose transcription is regulated by NF-B in a eukaryotic cell, the method comprising reducing NF-B activity in the cell such that expression of said viral gene is reduced.

4. The method of claim 3, wherein the viral gene is a cytomegalovirus (CMV), human immunodeficiency virus (HIV) or simian virus 40 (SV40) gene.

5. A method for reducing the level of expression of a cytokine gene whose transcription is regulated by NF-B in a eukaryotic cell comprising reducing NF-B activity in the cell such that expression of said cytokine gene is reduced.

6. A method for diminishing induced NF-B-mediated intracellular signaling comprising reducing NF-B activity in cells such that NF-B-mediated intracellular signaling is diminished.

7. A method for modifying effects of external influences on a eukaryotic cell, which external influences induce NF-B-mediated intracellular signaling, the method comprising altering NF-B activity in the cells such that NF-B-mediated effects of external influences are modified.

8. The method of claim 7, wherein NF-B activity in the cell is reduced.

9. A method for reducing, in eukaryotic cells, the level of expression of genes which are activated by extracellular influences which induce NF-B-mediated intracellular signaling, the method comprising reducing NF-B activity in the cells such that expression of said genes is reduced.

10. A method for reducing the effects of bacterial infection on mammalian cells comprising reducing NF-B activity in mammalian cells so as to reduce bacterial lipopolysaccharide-induced gene expression in the mammalian cells.

11. A method for reducing the effects of viral infection on mammalian cells comprising reducing NF-B activity in mammalian cells so as to reduce virus-mediated gene expression in the mammalian cells.

12. A method for reducing the effects of bacterial infection on mammalian immune cells comprising reducing NF-B activity in mammalian immune cells so as to reduce bacterial lipopolysaccharide-mediated stimulation of the immune cells.

13. A method for reducing the effects of bacterial lipopolysaccharide on mammalian cells comprising reducing NF-B activity in the cells so as to reduce bacterial lipopolysaccharide-induced gene expression in the cells.

14. A method for reducing bacterial lipopolysaccharide-induced expression of cytokines in mammalian cells, which method comprises reducing NF-B activity in the cells so as to reduce bacterial lipopolysaccharide-induced expression of said cytokines in the cells.

15. A method for reducing bacterial lipopolysaccharide-induced expression of Tumor Necrosis Factor- in mammalian cells, which method comprises reducing NF-B activity in the cells so as to reduce bacterial lipopolysaccharide-induced expression of Tumor Necrosis Factor- in the cells.

16. A method for reducing bacterial lipopolysaccharide-mediated stimulation of immune cells, which method comprises reducing NF-B activity in the cells so as to reduce bacterial lipopolysaccharide-mediated stimulation of the immune cells.

17. A method for reducing bacterial-induced NF-B signaling in cells, which method comprises reducing NF-B activity in the cells so as to reduce bacterial-induced NF-B signaling in the cells.

18. A method for reducing Interleukin-1 or Tumor Necrosis Factor- activity in mammalian cells comprising reducing NF-B activity in the cells so as to reduce intracellular signaling caused by Interleukin-1 or Tumor Necrosis Factor- in the cells.

19. A method for reducing bacterial lipopolysaccharide-induced nuclear translocation of NF-B in eukaryotic cells comprising inhibiting one or more of: (a) modification of an IB protein which reduces binding to NF-B, (b) degradation of an IB protein, or (c) dissociation of NF-B-IB complexes so as to reduce nuclear translocation of NF-B in the cells.

20. The method of claim 1 wherein NF-B activity is reduced by decreasing the level of NF-B not bound in an NF-B:IB complex.

21. The method of claim 1 wherein NF-B activity is reduced by inhibiting the passage of NF-B into the nucleus of cells.

22. The method of claim 1, wherein NF-B activity is reduced by inhibiting modification of an IB protein, which modification otherwise reduces IB binding to NF-B.

23. The method of claim 1, wherein NF-B activity is reduced by inhibiting degradation of an IB protein.

24. The method of claim 1, wherein NF-B activity is reduced by inhibiting dissociation of NF-B:IB complexes.

25. The method of claim 1 wherein reducing NF-B activity comprises reducing binding of NF-B to NF-B recognition sites on genes which are transcriptionally regulated by NF-B.

26. The method of claim 1, carried out on mammalian cells.

27. The method of claim 1, carried out on human cells.

28. The method of claim 26 or 27, carried out on immune cells.

29. The-method of claim 26 or 27 carried out on lymphoid cells.

30. The method of claim 26 or 27, carried out on liver cells.

31. The method of claim 2 wherein NF-B activity is reduced by decreasing the level of NF-B not bound in an NF-B:IB complex.

32. The method of claim 2 wherein NF-B activity is reduced by inhibiting the passage of NF-B into the nucleus of cells.

33. The method of claim 2, wherein NF-B activity is reduced by inhibiting modification of an I-B protein, which modification otherwise reduces IB binding to NF-B.

34. The method of claim 2, wherein NF-B activity is reduced by inhibiting degradation of an IB protein.

35. The method of claim 2, wherein NF-B activity is reduced by inhibiting dissociation of NF-B:IB complexes.

36. The method of claim 2 wherein reducing NF-B activity comprises reducing binding of NF-B to NF-B recognition sites on genes which are transcriptionally regulated by NF-B.

37. The method of claim 2, carried out on mammalian cells.

38. The method of claim 2, carried out on human cells.

39. The method of claim 37 or 38, carried out on immune cells.

40. The method of claim 37 or 38, carried out on lymphoid cells.

41. The method of claim 37 or 38, carried out on liver cells.

42. The method of claim 3 wherein NF-B activity is reduced by decreasing the level of NF-B not bound in an NF-B:IB complex.

43. The method of claim 3 wherein NF-B activity is reduced by inhibiting the passage of NF-B into the nucleus of cells.

44. The method of claim 3, wherein NF-B activity is reduced by inhibiting modification of an I-B protein, which modification otherwise reduces IB binding to NF-B.

45. The method of claim 3, wherein NF-B activity is reduced by inhibiting degradation of an IB protein.

46. The method of claim 3, wherein NF-B activity is reduced by inhibiting dissociation of NF-B:IB complexes.

47. The method of claim 3 wherein reducing NF-B activity comprises reducing binding of NF-B to NF-B recognition sites on genes which are transcriptionally regulated by NF-B.

48. The method of claim 3, carried out on mammalian cells.

49. The method of claim 3, carried out on human cells.

50. The method of claim 48 or 49, carried out on immune cells.

51. The method of claim 48 or 49, carried out on lymphoid cells.

52. The method of claim 48 or 49, carried out on liver cells.

53. The method of claim 5 wherein NF-B activity is reduced by decreasing the level of NF-B not bound in an NF-B:IB complex.

54. The method of claim 5 wherein NF-B activity is reduced by inhibiting the passage of NF-B into the nucleus of cells.

55. The method of claim 5, wherein NF-B activity is reduced by inhibiting modification of an IB protein, which modification otherwise reduces IB binding to NF-B.

56. The method of claim 5, wherein NF-B activity is reduced by inhibiting degradation of an IB protein.

57. The method of claim 5, wherein NF-B activity is reduced by inhibiting dissociation of NF-B:IB complexes.

58. The method of claim 5 wherein reducing NF-B activity comprises reducing binding of NF-B to NF-B recognition sites on genes which are transcriptionally regulated by NF-B.

59. The method of claim 5, carried out on mammalian cells.

60. The method of claim 5, carried out on human cells.

61. The method of claim 59 or 60, carried out on immune cells.

62. The method of claim 59 or 60, carried out on lymphoid cells.

63. The method of claim 59 or 60, carried out on liver cells.

64. The method of claim 6 wherein NF-B activity is reduced by decreasing the level of NF-B not bound in an NF-B:IB complex.

65. The method of claim 6 wherein NF-B activity is reduced by inhibiting the passage of NF-B into the nucleus of cells.

66. The method of claim 6, wherein NF-B activity is reduced by inhibiting modification of an IB protein, which modification otherwise reduces IB binding to NF-B.

67. The method of claim 6, wherein NF-B activity is reduced by inhibiting degradation of an IB protein.

68. The method of claim 6, wherein NF-B activity is reduced by inhibiting dissociation of NF-B:IB complexes.

69. The method of claim 6 wherein reducing NF-B activity comprises reducing binding of NF-B to NF-B recognition sites on genes which are transcriptionally regulated by NF-B.

70. The method of claim 6, carried out on mammalian cells.

71. The method of claim 6, carried out on human cells.

72. The method of claim 70 or 71, carried out on immune cells.

73. The method of claim 70 or 71, carried out on lymphoid cells.

74. The method of claim 70 or 71, carried out on liver cells.

75. The method of claim 8 wherein NF-B activity is reduced by decreasing the level of NF-B not bound in an NF-B:IB complex.

76. The method of claim 8 wherein NF-KB activity is reduced by inhibiting the passage of NF-B into the nucleus of cells.

77. The method of claim 8, wherein NF-B activity is reduced by inhibiting modification of an IB protein, which modification otherwise reduces IB binding to NF-B.

78. The method of claim 8, wherein NF-B activity is reduced by inhibiting degradation of an IB protein.

79. The method of claim 8, wherein NF-B activity is reduced by inhibiting dissociation of NF-B:IB complexes.

80. The method of claim 8 wherein reducing NF-B activity comprises reducing binding of NF-B to NF-B recognition sites on genes which are transcriptionally regulated by NF-B.

81. The method of claim 7, carried out on mammalian cells.

82. The method of claim 8, carried out on mammalian cells.

83. The method of claim 7, carried out on human cells.

84. The method of claim 8, carried out on human cells.

85. The method of any of claims 81-84, carried out on immune cells.

86. The method of any of claims 81-84, carried out on lymphoid cells.

87. The method of any of claims 81-84, carried out on liver cells.

88. The method of claim 9 wherein NF-B activity is reduced by decreasing the level of NF-B not bound in an NF-B:IB complex.

89. The method of claim 9 wherein NF-B activity is reduced by inhibiting the passage of NF-B into the nucleus of cells.

90. The method of claim 9, wherein NF-B activity is reduced by inhibiting modification of an IB protein, which modification otherwise reduces IB binding to NF-B.

91. The method of claim 9, wherein NF-B activity is reduced by inhibiting degradation of an IB protein.

92. The method of claim 9, wherein NF-B activity is reduced by inhibiting dissociation of NF-B:IB complexes.

93. The method of claim 9 wherein reducing NF-B activity comprises reducing binding of NF-B to NF-B recognition sites on genes which are transcriptionally regulated by NF-B.

94. The method of claim 9, carried out on mammalian cells.

95. The method of claim 9, carried out on human cells.

96. The method of claim 94 or 95, carried out on immune cells.

97. The method of claim 94 or 95, carried out on lymphoid cells.

98. The method of claim 94 or 95, carried out on liver cells.

99. The method of claim 10 wherein NF-B activity is reduced by decreasing the level of NF-B not bound in an NF-B:IB complex.

100. The method of claim 10 wherein NF-B activity is reduced by inhibiting the passage of NF-B into the nucleus of cells.

101. The method of claim 10, wherein NF-B activity is reduced by inhibiting modification of an IB protein, which modification otherwise reduces IB binding to NF-B.

102. The method of claim 10, wherein NF-B activity is reduced by inhibiting degradation of an IB protein.

103. The method of claim 10, wherein NF-B activity is reduced by inhibiting dissociation of NF-B:IB complexes.

104. The method of claim 10 wherein reducing NF-B activity comprises reducing binding of NF-B to NF-B recognition sites on genes which are transcriptionally regulated by NF-B.

105. The method of claim 10, carried out on human cells.

106. The method of claim 11, carried out on immune cells.

107. The method of claim 11, carried out on lymphoid cells.

108. The method of claim 11, carried out on liver cells.

109. The method of claim 11 wherein NF-B activity is reduced by decreasing the level of NF-B not bound in an NF-B:IB complex.

110. The method of claim 11 wherein NF-B activity is reduced by inhibiting the passage of NF-B into the nucleus of cells.

111. The method of claim 11, wherein NF-B activity is reduced by inhibiting modification of an IB protein, which modification otherwise reduces IB binding to NF-B.

112. The method of claim 11, wherein NF-B activity is reduced by inhibiting degradation of an IB protein.

113. The method of claim 11, wherein NF-B activity is reduced by inhibiting dissociation of NF-B:IB complexes.

114. The method of claim 11 wherein reducing NF-B activity comprises reducing binding of NF-B to NF-B recognition sites on genes which are transcriptionally regulated by NF-B.

115. The method of claim 11, carried out on human cells.

116. The method of claim 11 or 115, carried out on immune cells.

117. The method of claim 11 or 115, carried out on lymphoid cells.

118. The method of claim 11 or 115, carried out on liver cells.

119. The method of claim 12 wherein NF-B activity is reduced by decreasing the level of NF-B not bound in an NF-B:IB complex.

120. The method of claim 12 wherein NF-B activity is reduced by inhibiting the passage of NF-B into the nucleus of cells.

121. The method of claim 12, wherein NF-B activity is reduced by inhibiting modification of an IB protein, which modification otherwise reduces IB binding to NF-B.

122. The method of claim 12, wherein NF-B activity is reduced by inhibiting degradation of an IB protein.

123. The method of claim 12, wherein NF-B activity is reduced by inhibiting dissociation of NF-B:IB complexes.

124. The method of claim 12 wherein reducing NF-B activity comprises reducing binding of NF-B to NF-B recognition sites on genes which are transcriptionally regulated by NF-B.

125. The method of claim 12, carried out on human immune cells.

126. The method of claim 12, carried out on lymphoid cells.

127. The method of claim 125, carried out on lymphoid cells.

128. The method of claim 13 wherein NF-B activity is reduced by decreasing the level of NF-B not bound in an NF-B:IB complex.

129. The method of claim 13 wherein NF-B activity is reduced by inhibiting the passage of NF-B into the nucleus of cells.

130. The method of claim 13, wherein NF-B activity is reduced by inhibiting modification of an IB protein, which modification otherwise reduces IB binding to NF-B.

131. the method of claim 13, wherein NF-B activity is reduced by inhibiting degradation of an IB protein.

132. The method of claim 13, wherein NF-B activity is reduced by inhibiting dissociation of NF-B:IB complexes.

133. The method of claim 13 wherein reducing NF-B activity comprises reducing binding of NF-B to NF-B recognition sites on genes which are transcriptionally regulated by NF-B.

134. The method of claim 13, carried out on human cells.

135. The method of claim 13, carried out on immune cells.

136. The method of claim 134, carried out on immune cells.

137. The method of claim 13 or 134, carried out on lymphoid cells.

138. The method of claim 13 or 134, carried out on liver cells.

139. The method of claim 14 wherein NF-B activity is reduced by decreasing the level of NF-B not bound in an NF-B:IB complex.

140. The method of claim 14 wherein NF-B activity is reduced by inhibiting the passage of NF-B into the nucleus of cells.

141. The method of claim 14, wherein NF-B activity is reduced by inhibiting modification of an IB protein, which modification otherwise reduces IB binding to NF-B.

142. The method of claim 14, wherein NF-B activity is reduced by inhibiting degradation of an IB protein.

143. The method of claim 14, wherein NF-B activity is reduced by inhibiting dissociation of NF-B:IB complexes.

144. The method of claim 14 wherein reducing NF-B activity comprises reducing binding of NF-B to NF-B recognition sites on genes which are transcriptionally regulated by NF-B.

145. The method of claim 14, carried out on human cells.

146. The method of claim 14 or 145, carried out on immune cells.

147. The method of claim 14 or 145, carried out on lymphoid cells.

148. The method of claim 14 or 145, carried out on liver cells.

149. The method of claim 15 wherein NF-B activity is reduced by decreasing the level of NF-B not bound in an NF-B:IB complex.

150. The method of claim 15 wherein NF-B activity is reduced by inhibiting the passage of NF-B into the nucleus of cells.

151. The method of claim 15, wherein NF-B activity is reduced by inhibiting modification of an IB protein, which modification otherwise reduces IB binding to NF-B.

152. The method of claim 15, wherein NF-B activity is reduced by inhibiting degradation of an IB protein.

153. The method of claim 15, wherein NF-B activity is reduced by inhibiting dissociation of NF-B:IB complexes.

154. The method of claim 15 wherein reducing NF-B activity comprises reducing binding of NF-B to NF-B recognition sites on genes which are transcriptionally regulated by NF-B.

155. The method of claim 15, carried out on human cells.

156. The method of claim 15 of 155, carried out on immune cells.

157. The method of claim 15 or 155, carried out on lymphoid cells.

158. The method of claim 15 or 155, carried out on liver cells.

159. The method of claim 16 wherein NF-B activity is reduced by decreasing the level of NF-B not bound in an NF-B:IB complex.

160. The method of claim 16 wherein NF-B activity is reduced by inhibiting the passage of NF-B into the nucleus of cells.

161. The method of claim 16, wherein NF-B activity is reduced by inhibiting modification of an IB protein, which modification otherwise reduces IB binding to NF-B.

162. The method of claim 16, wherein NF-B activity is reduced by inhibiting degradation of an IB protein.

163. The method of claim 16, wherein NF-B activity is reduced by inhibiting dissociation of NF-B:IB complexes.

164. The method of claim 16 wherein reducing NF-B activity comprises reducing binding of NF-B to NF-B recognition sites on genes which are transcriptionally regulated by NF-B.

165. The method of claim 16, carried out on human cells.

166. The method of claim 16 or 165, carried out on lymphoid cells.

167. The method of claim 17 wherein NF-B activity is reduced by decreasing the level of NF-B not bound in an NF-B:IB complex.

168. The method of claim 17 wherein NF-B activity is reduced by inhibiting the passage of NF-B into the nucleus of cells.

169. The method of claim 17, wherein NF-B activity is reduced by inhibiting modification of an IB protein, which modification otherwise reduces IB binding to NF-B.

170. The method of claim 17, wherein NF-B activity is reduced by inhibiting degradation of an IB protein.

171. The method of claim 17, wherein NF-B activity is reduced by inhibiting dissociation of NF-B:IB complexes.

172. The method of claim 17 wherein reducing NF-B activity comprises reducing binding of NF-B to NF-B recognition sites on genes which are transcriptionally regulated by NF-B.

173. The method of claim 17, carried out on human cells.

174. The method of claim 17 or 173, carried out on immune cells.

175. The method of claim 17 or 173, carried out on lymphoid cells.

176. The method of claim 17 or 173, carried out on liver cells.

177. The method of claim 18 wherein NF-B activity is reduced by decreasing the level of NF-B not bound in an NF-B:IB complex.

178. The method of claim 18 wherein NF-B activity is reduced by inhibiting the passage of NF-B into the nucleus of cells.

179. The method of claim 18, wherein NF-B activity is reduced by inhibiting modification of an IB protein, which modification otherwise reduces IB binding to NF-B.

180. The method of claim 18, wherein NF-B activity is reduced by inhibiting degradation of an IB protein.

181. The method of claim 18, wherein NF-B activity is reduced by inhibiting dissociation of NF-B:IB complexes.

182. The method of claim 18 wherein reducing NF-B activity comprises reducing binding of NF-B to NF-B recognition sites on genes which are transcriptionally regulated by NF-B.

183. The method of claim 18, carried out on human cells.

184. The method of claim 18 or 183, carried out on immune cells.

185. The method of claim 18 or 183, carried out on lymphoid cells.

186. The method of claim 18 or 183, carried out on liver cells.

187. The method of claim 19, carried out on mammalian cells.

188. The method of claim 19, carried out on human cells.

189. The method of claim 187 or 188, carried out on immune cells.

190. The method of claim 187 or 188, carried out on lymphoid cells.

191. The method of claim 193 or 194, carried out on liver cells.

192. The method of claim 4 wherein NF-B activity is reduced by decreasing the level of NF-B not bound in an NF-B:IB complex.

193. The method of claim 4 wherein NF-B activity is reduced by inhibiting the passage of NF-B into the nucleus of cells.

194. The method of claim 4, wherein NF-B activity is reduced by inhibiting modification of an IB protein, which modification otherwise reduces IB binding to NF-B.

195. The method of claim 4, wherein NF-B activity is reduced by inhibiting degradation of an IB protein.

196. The method of claim 4, wherein NF-B activity is reduced by inhibiting dissociation of NF-B:IB complexes.

197. The method of claim 4 wherein reducing NF-B activity comprises reducing binding of NF-B to NF-B recognition sites on genes which are transcriptionally regulated by NF-B.

198. The method of claim 4, carried out on mammalian cells.

199. The method of claim 4, carried out on human cells.

200. The method of claim 198 or 199, carried out on immune cells.

201. The method of claim 198 or 199, carried out on lymphoid cells.

202. The method of claim 198 or 199, carried out on liver cells.

203. A method of inhibiting expression, in a mammalian cell, of a gene whose transcriptional activity is activated by binding of NF-B to said gene, comprising introducing a nucleic acid decoy molecule into the cell in an amount sufficient to inhibit expression of the gene, which decoy includes a NF-B binding site that binds to NF-B.