ISOLATION AND CHARACTERIZATION OF A NEW GENE ENCODING A MEMBER OF THEHIRA FAMILY OF PROTEINS FROM DROSOPHILA-MELANOGASTER

The HIRA family of genes (named after yeast HIR genes; HIR is an acron ym for 'histone regulator') includes the yeast HIRI and HIR2 repressor s of histone gene transcription in S. cerevisiae, human TUPLE-1/HIRA, chicken HIRA, and mouse HIRA. Here, we describe a new member of the HI RA 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 transcri pt of 4.1 kb. Hybridization is strong in female adults, unfertilized e ggs and 0-3-h-old embryos, then diminishes, but is still detectable, d uring later stages of development and in adult males.;More specificall y, in-situ hybridization shows that Dhh transcripts, which are initial ly detected in nurse cells during mid-oogenesis, become localized to t he developing oocyte at high levels. Transcripts persist strongly duri ng early blastoderm stages then fade dramatically by 3 h of developmen t. The Dhh cDNA encodes an open reading frame of 1061 amino acids with high similarity scores to the HIRA polypeptides, as well as two hypot hetical polypeptides from C. elegans and S. pombe, in a protein databa se 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 rep eats plus a region with no homology outside of the family. The conserv ation of these homologous regions in HIRA-encoded proteins from evolut ionary distant organisms suggests that they are important for the acti vity of the members of the family. (C) 1998 Elsevier Science B.V. All rights reserved.