ALY, a context-dependent coactivator of LEF-1 and AML-1, is required for TCRalpha enhancer function.
LEF-1 is a transcription factor that participates in the regulation of the T-cell receptor alpha (TCR alpha) enhancer by facilitating the assembly of multiple proteins into a higher order nucleoprotein complex. The function of LEF-1 is dependent, in part, on the HMG domain that induces a sharp bend in the ... DNA helix, and on an activation domain that stimulates transcription only in a specific context of other enhancer-binding proteins. With the aim of gaining insight into the function of context-dependent activation domains, we cloned ALY, a novel LEF-1-interacting protein. ALY is a ubiquitously expressed, nuclear protein that specifically associates with the activation domains of LEF-1 and AML-1 (CBF alpha2, PEBP2 alpha(B), which is another protein component of the TCR alpha enhancer complex. In addition, ALY can increase DNA binding by both LEF-1 and AML proteins. Overexpression of ALY stimulates the activity of the TCR alpha enhancer complex reconstituted in transfected nonlymphoid HeLa cells, whereas down-regulation of ALY by anti-sense oligonucleotides virtually eliminates TCR alpha enhancer activity in T cells. Similar to LEF-1, ALY can stimulate transcription in the context of the TCR alpha enhancer but apparently not when tethered to DNA through an heterologous DNA-binding domain. We propose that ALY mediates context-dependent transcriptional activation by facilitating the functional collaboration of multiple proteins in the TCR alpha enhancer complex.
Mesh Terms:
Amino Acid Sequence, Animals, Base Sequence, Binding Sites, Cloning, Molecular, Core Binding Factor alpha Subunits, DNA-Binding Proteins, Enhancer Elements, Genetic, Humans, Hybrid Cells, Lymphoid Enhancer-Binding Factor 1, Molecular Sequence Data, Nuclear Proteins, RNA-Binding Proteins, Receptors, Antigen, T-Cell, alpha-beta, T-Lymphocytes, Transcription Factor AP-2, Transcription Factors, Transcriptional Activation, Yeasts
Amino Acid Sequence, Animals, Base Sequence, Binding Sites, Cloning, Molecular, Core Binding Factor alpha Subunits, DNA-Binding Proteins, Enhancer Elements, Genetic, Humans, Hybrid Cells, Lymphoid Enhancer-Binding Factor 1, Molecular Sequence Data, Nuclear Proteins, RNA-Binding Proteins, Receptors, Antigen, T-Cell, alpha-beta, T-Lymphocytes, Transcription Factor AP-2, Transcription Factors, Transcriptional Activation, Yeasts
Genes Dev.
Date: Mar. 01, 1997
PubMed ID: 9119228
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