Isolation and characterization of a new gene encoding a member of the HIRA family of proteins from Drosophila melanogaster

The HIRA family of genes (named after yeast HIR genes; HIR is an acronym for 'histone regulator') includes the yeast HIR1 and HIR2 repressors of histone gene transcription in S. celevisiae, human TUPLE-1/HIRA, chicken HIRA, and mouse HIRA. Here, we describe a new member of the HIRA family, Dhh, for the Drosophila homolog of HIRA. Northern analysis with poly (A)⁺ mRNA isolated from different developmental stages of Drosophila melanogaster shows hybridization with a single Dhh transcript of 4.1 kb. Hybridization is strong in female adults, unfertilized eggs and 0-3-h-old embryos, then diminishes, but is still detectable, during later stages of development and in adult males. More specifically, in-situ hybridization shows that Dhh transcripts, which are initially detected in nurse cells during mid-oogenesis, become localized to the developing oocyte at high levels. Transcripts persist strongly during early blastoderm stages then fade dramatically by 3 h of development. The Dhh cDNA encodes an open reading frame of 1061 amino acids with high similarity scores to the HIRA polypeptides, as well as two hypothetical polypeptides from C. elegans and S. pombe, in a protein database search. They all share three highly homologous regions: a WD-repeat cluster, a small domain with clustered positively charged amino acids, and a domain comprising two repeats with close resemblance to WD repeats plus a region with no homology outside of the family. The conservation of these homologous regions in HIRA-encoded proteins from evolutionary distant organisms suggests that they are important for the activity of the members of the family.