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Titolo:
Induction of germline transcription in the human TCR gamma locus by STAT5
Autore:
Lee, HC; Ye, SK; Honjo, T; Ikuta, K;
Indirizzi:
Kyoto Univ, Grad Sch Med, Dept Med Chem, Sakyo Ku, Kyoto 6068501, Japan Kyoto Univ Kyoto Japan 6068501 Med Chem, Sakyo Ku, Kyoto 6068501, Japan
Titolo Testata:
JOURNAL OF IMMUNOLOGY
fascicolo: 1, volume: 167, anno: 2001,
pagine: 320 - 326
SICI:
0022-1767(20010701)167:1<320:IOGTIT>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
RECEPTOR-DEFICIENT MICE; T-CELL DEVELOPMENT; INTERLEUKIN-7 RECEPTOR; ACCESSIBILITY CONTROL; GENE REARRANGEMENT; IL-7 RECEPTOR; V(D)J RECOMBINATION; BETA LOCUS; ALPHA; DIFFERENTIATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
32
Recensione:
Indirizzi per estratti:
Indirizzo: Ikuta, K Kyoto Univ, Grad Sch Med, Dept Med Chem, Sakyo Ku, Kyoto 6068501,Japan Kyoto Univ Kyoto Japan 6068501 , Sakyo Ku, Kyoto 6068501, Japan
Citazione:
H.C. Lee et al., "Induction of germline transcription in the human TCR gamma locus by STAT5", J IMMUNOL, 167(1), 2001, pp. 320-326

Abstract

TCR and Ig genes are assembled by V(D)J recombination during lymphocyte development. The enhancer and the germline promoter control the accessibilityof each locus for the common recombinase activity. In the mouse TCR gamma locus, STAT5 proteins activated by the IL-7R interact with consensus motifsin 5 ' regions of J gamma segments and induce germline transcription. To evaluate the role of STAT5 in controlling the accessibility of the TCR gammalocus, we characterized the germline transcription of human TCR gamma genes and compared it with mouse. We first demonstrated that J gamma -C gamma germline transcripts are induced in a cytokine-dependent human erythroleukemia cell line. STAT consensus motifs are present in 5 ' regions of J-gamma1.1 and J gamma2.1 gene segments, and activated STAT5 binds to these motifs. By using a reporter assay, we showed that the J gamma1.1 germline promoter is transactivated by STAT5 and that mutations in any of the two STAT motifsabrogate this activity. Thus, this study demonstrates that STAT5 induces germline transcription in the TCR gamma locus of both mouse and human and suggests the possibility that this mechanism may play an essential role in controlling the TCR gamma locus accessibility. In addition, STAT motifs are conserved among 5 ' J gamma germline promoters, 3 ' enhancers, and a locus control region-like element, HsA, in both mouse and human TCR gamma loci, indicating the possibility that IL-7R/STAT5 signaling probably controls the locus-wide accessibility through these elements.

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Documento generato il 28/01/20 alle ore 21:51:45