HELIX LOOP HELIX TRANSCRIPTION FACTOR-E47 ACTIVATES GERM-LINE IMMUNOGLOBULIN HEAVY-CHAIN GENE-TRANSCRIPTION AND REARRANGEMENT IN A PRE-T-CELL LINE
HELIX LOOP HELIX TRANSCRIPTION FACTOR-E47 ACTIVATES GERM-LINE IMMUNOGLOBULIN HEAVY-CHAIN GENE-TRANSCRIPTION AND REARRANGEMENT IN A PRE-T-CELL LINE
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DOI：
10.1101/gad.5.8.1367
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发表时间：
1991-08-01
影响因子：
10.5
通讯作者：
BALTIMORE, D
中科院分区：
文献类型：
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作者：
SCHLISSEL, M;VORONOVA, A;BALTIMORE, D
E47是一种螺旋-环-螺旋转录因子，与免疫球蛋白重链和kappa-轻链基因增强子结合。其他这种类型的蛋白质也参与了细胞类型的确定。通过在前T细胞系2017中过表达编码E47的cDNA，测试了E47在B细胞发育中的可能作用。我们发现，在这些稳定的转染体中，胚系重链基因转录本被戏剧性地激活，并同样大量地诱导免疫球蛋白D到J重排，这是B细胞发展中公认的第一步。胚系kappa轻链基因的转录和重排没有受到影响，但重组激活基因rag-1和rag-2以及淋巴组织特异性转录因子oct-2的转录增加。然而，这些T细胞没有转录它们重排的DJ等位基因，也没有进展到重链基因组装的下一阶段，即V-to-DJ重排。由于转录因子E47可以诱导前T细胞进行B细胞分化，因此它可能是B细胞发育早期的关键决定因素。
E47 is a helix-loop-helix transcription factor that binds to sites in the immunoglobulin heavy-chain and kappa-light-chain gene enhancers. Other proteins of this type are involved in cell-type determination. A possible role for E47 in B-cell development was tested by overexpressing a cDNA encoding E47 in the pre-T-cell line 2017. We found a dramatic activation of a germ-line heavy-chain gene transcript in these stable transfectants and an equally large induction of immunoglobulin D-to-J rearrangement, the first recognized step in B-cell development. Germ-line kappa-light-chain gene transcription and rearrangement were unaffected, but transcription of the recombination-activating genes RAG-1 and RAG-2 and the lymphoid-specific transcription factor Oct-2 was increased. These T cells did not transcribe their rearranged DJ alleles, however, and failed to progress to the next stage of heavy-chain gene assembly, V-to-DJ rearrangement. Because transcription factor E47 can induce pre-T cells to carry out events of B-cell differentiation, it may be a crucial determinant of the earliest stages of B-cell development.