ALY, A CONTEXT-DEPENDENT COACTIVATOR OF LEF-1 AND AML-1, IS REQUIRED FOR TCR-ALPHA 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 as sembly of multiple proteins into a higher order nucleoprotein complex. The function of LEE-I is dependent, in part, on the HMG domain that i nduces a sharp bend in the DNA helix, and on an activation domain that stimulates transcription only in a specific contest of other enhancer -binding proteins. With the aim of gaining insight into the function o f context-dependent activation domains, we cloned ALY, a novel LEF-1-i nteracting protein. ALY is a ubiquitously expressed, nuclear protein t hat specifically associates with the activation domains of LEF-1 and A ML-1 (CBF alpha 2, 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 stimulat es the activity of the TCR alpha enhancer complex reconstituted in tra nsfected nonlymphoid HeLa cells, whereas down-regulation of ALY by ant i-sense oligonucleotides virtually eliminates TCR alpha enhancer activ ity in T cells. Similar to LEF-1, ALY can stimulate transcription in t he contest 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 en hancer complex.