YY1 helps to bring loose ends together

Ubiquitously expressed transcription factor Yin Yang 1 (YY1) has long been believed to play some role in immunoglobulin gene regulation, because it associates with multiple Ig enhancer elements including the heavy-chain intron and 3′ enhancers as well as the Igκ 3′ enhancer (Park and Atchison 1991; Gordon et al. 2003). Early on, YY1 was noted to have bifunctional properties, in that it could either repress or activate transcription, depending on binding site context, protein interactions, or levels within the cell (Park and Atchison 1991; Seto et al. 1991; Shi et al. 1991; Lee et al. 1994 1995; Bushmeyer et al. 1995). Numerous mechanisms of YY1 transcriptional control were observed and a number of activation/repression models were proposed (Galvin and Shi 1997). YY1 function in transcription at the Ig loci was enigmatic, however, because no evidence exists for differential expression of YY1 during B-cell development, and deletion of enhancer YY1-binding sites had a marginal impact on enhancer activity as measured by transient expression assays (Park and Atchison 1991). It was generally assumed that YY1 might control some aspect of chromatin structure at the Ig loci not completely recapitulated by transient expression assays.

Over the 16 years since its discovery, a very large number of genes regulated by YY1 were identified (Shrivastava and Calame 1994; Thomas and Seto 1999; Gordon et al. 2006). In addition, YY1 was observed to interact with a large number of proteins including coactivators, corepressors, and other transcription factors (Thomas and Seto 1999; Gordon et al. 2006). More recently, YY1 was implicated in cell cycle control, oncogenesis, imprinting control, X-chromosome inactivation, and Polycomb Group (PcG) function (Sui et al. 2004; Gordon et al. 2006; Kim et al. 2006, 2007; Donohoe et al. 2007). The huge numbers …