Dynamic interplay of transcriptional machinery and chromatin regulates "late" expression of the chemokine RANTES in T lymphocytes.
The chemokine RANTES (regulated upon activation normal T cell expressed and secreted) is expressed "late" (3 to 5 days) after activation in T lymphocytes. In order to understand the molecular events that accompany changes in gene expression, a detailed analysis of the interplay between transcriptional machinery and chromatin on the RANTES promoter over time was undertaken. Krüppel-like factor 13 (KLF13), a sequence-specific DNA binding transcription factor, orchestrates the induction of RANTES expression in T lymphocytes by ordered recruitment of effector molecules, including Nemo-like kinase, p300/cyclic AMP response element binding protein (CBP), p300/CBP-associated factor, and Brahma-related gene 1, that initiate sequential changes in phosphorylation and acetylation of histones and ATP-dependent chromatin remodeling near the TATA box of the RANTES promoter. These events recruit RNA polymerase II to the RANTES promoter and are responsible for late expression of RANTES in T lymphocytes. Therefore, KLF13 is a key regulator of late RANTES expression in T lymphocytes.
Ahn
Yong-Tae
YT
Division of Immunology and Transplantation Biology, Department of Pediatrics, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305-5164, USA.
Huang
Boli
B
McPherson
Lisa
L
Clayberger
Carol
C
Krensky
Alan M
AM
D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology*; D018946:Chemokine CCL5 / Q000096:biosynthesis* / Q000235:genetics; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007700:Kinetics; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000502:physiology*; D008213:Lymphocyte Activation; D008954:Models, Biological; D011401:Promoter Regions, Genetic; D012319:RNA Polymerase II / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D013601:T-Lymphocytes / Q000378:metabolism*; D013997:Time Factors; D014158:Transcription, Genetic; D050880:p300-CBP Transcription Factors / Q000378:metabolism
D018797:Cell Cycle Proteins; D018946:Chemokine CCL5; D002843:Chromatin; C486423:KLF13 protein, human; D051741:Kruppel-Like Transcription Factors; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D050880:p300-CBP Transcription Factors; D012319:RNA Polymerase II