Investigation of the Developmental Requirements of Drosophila HP1 and Insulator Protein Partner, HIPP1

Drosophila Suppressor of Hairy-wing [Su(Hw)] is a multifunctional zinc finger DNA binding protein. Transcriptional regulation by Su(Hw) is essential in the ovary and testis, where Su(Hw) functions primarily as a repressor. Recently, the HP1a and Insulator Partner Protein 1 (HIPP1) was found to extensively co-localize with Su(Hw) and other insulator binding proteins in euchromatic regions of the genome, and with Heterochromatin Protein 1a (HP1a) in heterochromatic regions. As HIPP1 is the homolog of the human co-repressor Chromodomain Y-Like (CDYL), we tested its requirement in establishing transcriptional repression in flies. To this end, we generated multiple Hipp1 null alleles and a tagged derivative of the endogenous gene (Hipp1(GFP)), using CRISPR mutagenesis. We show that HIPP1 is a widely expressed nuclear protein that is dispensable for viability, as well as female and male fertility. We find that HIPP1 and HP1a display minimum co-localization in interphase cells, and HP1a-dependent transcriptional repression of several reporter genes is HIPP1-independent, indicating that HIPP1 is not essential for HP1a-dependent heterochromatin formation. Despite Su(Hw) having a major role in promoting HIPP1 occupancy in euchromatin, we show that HIPP1 is dispensable for the transcriptional and insulator functions of Su(Hw), indicating that HIPP1 is not a critical Su(Hw) cofactor. Further studies are needed to clarify the role of HIPP1 in Drosophila development.