PMID- 10551799
OWN - NLM
STAT- MEDLINE
DCOM- 19991223
LR  - 20181113
IS  - 1052-2166 (Print)
IS  - 1555-3884 (Electronic)
IS  - 1052-2166 (Linking)
VI  - 8
IP  - 2
DP  - 1999
TI  - Constitutive and inducible in vivo protein-DNA interactions at the tumor necrosis 
      factor-alpha promoter in primary human T lymphocytes.
PG  - 115-27
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a key cytokine of lymphocytes with 
      major regulatory functions in immunomodulation, chronic inflammation, and septic 
      shock. However, only limited information on TNF promoter regulation in vivo in 
      primary lymphocytes is available. To determine and compare protein-DNA 
      interactions at the native TNF locus in primary lymphocytes, we analyzed the 
      human TNF-alpha promoter by ligation-mediated polymerase chain reaction (LM-PCR) 
      techniques. Accordingly, primary CD4+ T lymphocytes from peripheral blood were 
      cultured in the presence of various stimuli and analyzed by LM-PCR. Inducible in 
      vivo protein-DNA interactions at the TNF promoter were detected between -120 and 
      -70 bp of the human TNF promoter relative to the transcriptional start site. This 
      area includes binding sites for transcription factors such as ETS-1, NFAT, 
      ATF-2/c-jun, SP-1/Egr-1, and NF-kappaB. In contrast, no protein-DNA interactions 
      were observed at various binding sites with reported regulatory function in tumor 
      cell lines such as the k2 element, the NFAT site at -160, the AP1 site at -50, 
      and the SP1 site at -65. Additional mutagenesis and transfection studies 
      demonstrated that NF-kappaB and CREB/AP-1 are important regulators of inducible 
      TNF promoter activity in primary human T lymphocytes. These results provide novel 
      insights into the complex regulation of TNF gene transcription in primary T 
      lymphocytes in vivo by constitutive and inducible protein-DNA interactions that 
      appear to be at least partially different compared to previously characterized 
      tumor cell lines.
FAU - Becker, C
AU  - Becker C
AD  - Laboratory of Immunology, I. Medical Clinic, University of Mainz, Germany.
FAU - Barbulescu, K
AU  - Barbulescu K
FAU - Wirtz, S
AU  - Wirtz S
FAU - Meyer zum Buschenfelde, K H
AU  - Meyer zum Buschenfelde KH
FAU - Pettersson, S
AU  - Pettersson S
FAU - Neurath, M F
AU  - Neurath MF
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Gene Expr
JT  - Gene expression
JID - 9200651
RN  - 0 (Transcription Factors)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Base Sequence
MH  - Binding Sites
MH  - DNA/*metabolism
MH  - DNA Footprinting
MH  - Humans
MH  - Molecular Sequence Data
MH  - Mutagenesis, Site-Directed
MH  - Polymerase Chain Reaction
MH  - *Promoter Regions, Genetic
MH  - Response Elements
MH  - T-Lymphocytes/*metabolism
MH  - Transcription Factors/*metabolism
MH  - Tumor Necrosis Factor-alpha/biosynthesis/*genetics/*metabolism
PMC - PMC6157389
EDAT- 1999/11/07 00:00
MHDA- 1999/11/07 00:01
PMCR- 2018/09/26
CRDT- 1999/11/07 00:00
PHST- 1999/11/07 00:00 [pubmed]
PHST- 1999/11/07 00:01 [medline]
PHST- 1999/11/07 00:00 [entrez]
PHST- 2018/09/26 00:00 [pmc-release]
AID - GE-8-115 [pii]
PST - ppublish
SO  - Gene Expr. 1999;8(2):115-27.