Role for the mammalian transcription factor YY1 and its Drosophila homologue pho in regulation of replication-dependent histone gene expression

Expression of the highly conserved replication-dependent histone genes increases dramatically as a cell enters the DNA synthesis phase of the eukaryotic cell cycle. Requirements for normal histone gene expression in vivo include an element, designated alpha, located within the protein-encoding sequence of all four classes of nucleosomal histone genes. A yeast one-hybrid screen of a HeLa cell cDNA library identified the protein responsible for recognition of the mouse histone H3.2alpha sequence as the transcription factor Yin Yang 1 (YY1). Here we report that YY1 is required for the in vitro histone alpha DNA-protein interaction. In addition, mutation of the nucleotides required for the alpha-YY1 in vitro interaction also dramatically alters the cell cycle phase-specific up-regulation of the mouse H3.2 gene in vivo in stable transfectant CHO cells. We cloned the Drosophila homologue of YY1 and determined that it is encoded by the gene pleiohomeotic (pho ) by rescue of pho mutations using a heat-shock inducible dYY1 transgene. Also using this transgene we have determined that pho is specifically required during embryogenesis and just prior to metamorphosis for complete rescue of pho mutants. As in the mouse, we find DNA binding activity with the Drosophila H3.2alpha coding region element that is specific to the replication-dependent histone gene and not the H3.3 replication-independent gene. We also show that pho mutant embryos express 4-fold less histone mRNA than wild type embryos and that heat-shock induction of the dYY1 transgene results in a partial rescue of wild-type levels of histone H3 mRNA. Pho, like YY1 in the mouse, is required for normal high-level expression of the replication-dependent histone genes.