Studies of coat color mutants have greatly contributed to the discovery of genes 
that regulate melanocyte development and function. Here, we generated Yy1 
conditional knockout mice in the melanocyte-lineage and observed profound 
melanocyte deficiency and premature gray hair, similar to the loss of 
melanocytes in human piebaldism and Waardenburg syndrome. Although YY1 is a 
ubiquitous transcription factor, YY1 interacts with M-MITF, the Waardenburg 
Syndrome IIA gene and a master transcriptional regulator of melanocytes. YY1 
cooperates with M-MITF in regulating the expression of piebaldism gene KIT and 
multiple additional pigmentation genes. Moreover, ChIP-seq identified 
genome-wide YY1 targets in the melanocyte lineage. These studies mechanistically 
link genes implicated in human conditions of melanocyte deficiency and reveal 
how a ubiquitous factor (YY1) gains lineage-specific functions by co-regulating 
gene expression with a lineage-restricted factor (M-MITF)-a general mechanism 
which may confer tissue-specific gene expression in multiple lineages.