Kruppel-like transcription factor 13 regulates T lymphocyte survival in vivo.
Krüppel-like transcription factor (KLF)13, previously shown to regulate RANTES expression in vitro, is a member of the Krüppel- like family of transcription factors that controls many growth and developmental processes. To ascertain the function of KLF13 in vivo, Klf13-deficient mice were generated by gene targeting. As expected, activated T lymphocytes from Klf13(-/-) mice show decreased RANTES expression. However, these mice also exhibit enlarged thymi and spleens. TUNEL, as well as spontaneous and activation-induced death assays, demonstrated that prolonged survival of Klf13(-/-) thymocytes was due to decreased apoptosis. Microarray analysis suggests that protection from apoptosis-inducing stimuli in Klf13(-/-) thymocytes is due in part to increased expression of BCL-X(L), a potent antiapoptotic factor. This finding was confirmed in splenocytes and total thymocytes by real-time quantitative PCR and Western blot as well as in CD4+CD8- single-positive thymocytes by real-time quantitative PCR. Furthermore, EMSA and luciferase reporter assays demonstrated that KLF13 binds to multiple sites within the Bcl-X(L) promoter and results in decreased Bcl-X(L) promoter activity, making KLF13 a negative regulator of BCL-X(L).
Zhou
Meixia
M
Department of Pediatrics, Stanford University, 300 Pasteur Drive, Palo Alto, CA 94305, USA.
McPherson
Lisa
L
Feng
Dongdong
D
Song
An
A
Dong
Chen
C
Lyu
Shu-Chen
SC
Zhou
Lu
L
Shi
Xiaoyan
X
Ahn
Yong-Tae
YT
Wang
Demin
D
Clayberger
Carol
C
Krensky
Alan M
AM
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002470:Cell Survival / Q000235:genetics; D018946:Chemokine CCL5 / Q000032:analysis / Q000235:genetics; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000235:genetics; D008221:Lymphoid Tissue / Q000033:anatomy & histology; D051379:Mice; D018345:Mice, Knockout; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*; D051020:bcl-X Protein / Q000032:analysis / Q000037:antagonists & inhibitors / Q000235:genetics*
D018797:Cell Cycle Proteins; D018946:Chemokine CCL5; C486422:Klf13 protein, mouse; D051741:Kruppel-Like Transcription Factors; D012097:Repressor Proteins; D051020:bcl-X Protein