Transcriptional regulation of the mouse interleukin-2 receptor beta chain gene by Ets and Egr-1.
To clarify the mechanisms and factors involved in the regulation of mouse IL-2Rbeta gene expression, we isolated the 5'-flanking region of IL-2Rbeta gene and investigated the promoter activity. Here we elucidated the positive regulatory regions, the most potent of which are located between -50 to -30bp and -164 to -135bp. These regions contain a potentially functional Ets and Egr-1-binding sites whose mutations abrogate promoter activity. Data from electrophoretic mobility shift assay indicate that Ets and Egr-1, but not Sp1, bind to the positive regulatory regions, -50 to -30bp and -164 to -135bp, respectively. Furthermore, recruitment of Ets and Egr-1 at endogenous IL-2Rbeta promoter segments in an IL-2-dependent F7 cells was verified by the chromatin immunoprecipitation assay. This study for the first time delineates the molecular mechanisms underlying regulation of mouse IL-2Rbeta gene transcription by Ets family proteins, partially with Egr-1, and thereby further elucidates the molecular basis of lymphocyte activation and differentiation.
Ye
Sang-Kyu
SK
Department of Pharmacology, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-799, Republic of Korea.
Kim
Tack Joong
TJ
Won
Sung Sik
SS
Yoon
Taek Joon
TJ
Park
Tae Kyu
TK
Yoo
Yung Choon
YC
Kim
Yong-Nyun
YN
Lee
Hai Chon
HC
Ikuta
Koichi
K
Chung
Myung-Hee
MH
Lee
Kwang Ho
KH
D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D051766:Early Growth Response Protein 1; D005786:Gene Expression Regulation / Q000502:physiology*; D017874:Immediate-Early Proteins / Q000378:metabolism*; D053646:Interleukin-2 Receptor beta Subunit; D051379:Mice; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D050783:Proto-Oncogene Proteins c-ets; D018123:Receptors, Interleukin / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation / Q000502:physiology*
D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; C508022:Il2rb protein, mouse; D017874:Immediate-Early Proteins; D053646:Interleukin-2 Receptor beta Subunit; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D018123:Receptors, Interleukin; D014157:Transcription Factors