Role for a YY1-binding element in replication-dependent mouse histone gene expression

Expression of the highly conserved replication-dependent historic gene family increases dramatically as a cell enters the S phase of the eukaryotic cell cycle. Requirements for normal histone gene expression in vivo include an element, designated α, located within the protein-encoding sequence of nucleosomal histone genes. Mutation of 5 of 7 nucleotides of the mouse H3.2 α element to yield the sequence found in an H3.3 replication-independent variant abolishes the DNA-protein interaction in vitro and reduces expression fourfold in vivo. A yeast one-hybrid screen of a HeLa cell cDNA library identified the protein responsible for recognition of the histone H3.2 α sequence as the transcription factor Yin Yang 1 (YY1). YY1 is a ubiquitous and highly conserved transcription factor reported to be involved in both activation and repression of gene expression. Here we report that the in vitro histone α DNA-protein interaction depends on YY1 and that mutation of the nucleotides required for the in vitro histone α DNA-YY1 interaction alters the cell cycle phase-specific up-regulation of the mouse H3.2 gene in vivo. Because all mutations or deletions of the histone α sequence both abolish interactions in vitro and cause an in vivo decrease in histone gene expression, the recognition of the historic α element by YY1 is implicated in the correct temporal regulation of replication-dependent histone gene expression in vivo.