TY - JOUR
T1 - Binding of thymic factors to the conserved decanucleotide promoter element of the T-cell receptor Vβ gene is developmentally regulated and is absent in SCID mice
AU - Lanier, E. R.
AU - Brown, R. M.
AU - Kraig, E.
PY - 1991
Y1 - 1991
N2 - The gene segments encoding the β chain of the T-cell antigen receptor undergo rearrangement in a precise developmental order: a Dβ gene segment joins to a Jβ gene segment prior to the rearrangement of a Vβ gene segment to join the D/Jβ fusion. Current evidence suggests that the rearrangement of Vβ is restricted to T cells, whereas D-to-Jβ rearrangements may occur in both B and T cells. Thus, the T-cell specificity seems to be regulated by the Vβ coding region or its 5′ flanking sequence. In support of this hypothesis, evidence is provided for thymus-specific factors that bind a highly conserved 10-base-pair (decamer) sequence that is an essential promoter element in mouse and human Vβ genes. The presence of decamer-binding activities was assayed by gel mobility-shift analysis using protein extracts from thymus, spleen, and nonlymphoid organs of adult mice. Two shifted complexes, designated T2 and T3, were seen only when the decamer was incubated with extracts from thymus. When extracts from mice of various gestational ages were tested for decamer-binding activity, one of the thymus-specific complexes, T2, was first detected at day 16; this coincides with the time of initial activation of the Vβ locus. No decamer-binding activity was detected in extracts prepared from the thymuses of SCID (severe combined immunodeficiency) mice, which characteristically fail to rearrange these genes. Moreover, neither T2 nor T3 was detectable with extracts from spleen or from two T-cell lines that express the β chain; this suggests that the presence of these two complexes is not absolutely required for transcription of the T-cell receptor β locus. We conclude that there are tissue-specific and devdopmentally regulated factors that form complexes with the decamer sequence 5′ of Vβ; these may represent initiation factors that control the activation of germ-line T-cell receptor Vβ genes for transcription and/or rearrangement. (.
AB - The gene segments encoding the β chain of the T-cell antigen receptor undergo rearrangement in a precise developmental order: a Dβ gene segment joins to a Jβ gene segment prior to the rearrangement of a Vβ gene segment to join the D/Jβ fusion. Current evidence suggests that the rearrangement of Vβ is restricted to T cells, whereas D-to-Jβ rearrangements may occur in both B and T cells. Thus, the T-cell specificity seems to be regulated by the Vβ coding region or its 5′ flanking sequence. In support of this hypothesis, evidence is provided for thymus-specific factors that bind a highly conserved 10-base-pair (decamer) sequence that is an essential promoter element in mouse and human Vβ genes. The presence of decamer-binding activities was assayed by gel mobility-shift analysis using protein extracts from thymus, spleen, and nonlymphoid organs of adult mice. Two shifted complexes, designated T2 and T3, were seen only when the decamer was incubated with extracts from thymus. When extracts from mice of various gestational ages were tested for decamer-binding activity, one of the thymus-specific complexes, T2, was first detected at day 16; this coincides with the time of initial activation of the Vβ locus. No decamer-binding activity was detected in extracts prepared from the thymuses of SCID (severe combined immunodeficiency) mice, which characteristically fail to rearrange these genes. Moreover, neither T2 nor T3 was detectable with extracts from spleen or from two T-cell lines that express the β chain; this suggests that the presence of these two complexes is not absolutely required for transcription of the T-cell receptor β locus. We conclude that there are tissue-specific and devdopmentally regulated factors that form complexes with the decamer sequence 5′ of Vβ; these may represent initiation factors that control the activation of germ-line T-cell receptor Vβ genes for transcription and/or rearrangement. (.
KW - DNA-binding protein
KW - Gene rearrangement
KW - Mobility shift
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M3 - Article
C2 - 1832773
AN - SCOPUS:0025916263
SN - 0027-8424
VL - 88
SP - 8131
EP - 8135
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 18
ER -