ROLE FOR A YY1-BINDING ELEMENT IN REPLICATION-DEPENDENT MOUSE HISTONEGENE-EXPRESSION

Expression of the highly conserved replication-dependent histone gene family increases dramatically as a cell enters the S phase of the euka ryotic cell cycle. Requirements for normal histone gene expression in vivo include an element, designated alpha, located within the protein- encoding sequence of nucleosomal histone genes. Mutation of 5 of 7 nuc leotides of the mouse H3.2 alpha element to yield the sequence found i n an H3.3 replication-independent variant abolishes the DNA-protein in teraction in vitro and reduces expression fourfold in vivo, A yeast on e-hybrid screen of a HeLa cell cDNA library identified the protein res ponsible for recognition of the histone H3.2 alpha sequence as the tra nscription factor Yin Yang 1 (YY1). YY1 is a ubiquitous and highly con served transcription factor reported to be involved in both activation and repression of gene expression. Here we report that the in vitro h istone alpha DNA-protein interaction depends on YY1 and that mutation of the nucleotides required for the in vitro histone alpha DNA-YY1 int eraction alters the cell cycle phase-specific up-regulation of the mou se H3.2 gene in vivo. Because all mutations or deletions of the histon e a sequence both abolish interactions in vitro and cause an in vivo d ecrease in histone gene expression, the recognition of the histone alp ha element by YY1 is implicated in the correct temporal regulation of replication-dependent histone gene expression in vivo.