RT Journal Article SR Electronic T1 Differential Contributions of DNA-Binding Proteins to Polycomb Response Element Activity at the Drosophila giant Gene JF Genetics JO Genetics FD Genetics Society of America SP 623 OP 634 DO 10.1534/genetics.119.302981 VO 214 IS 3 A1 Ghotbi, Elnaz A1 Lackey, Kristina A1 Wong, Vicki A1 Thompson, Katie T. A1 Caston, Evan G. A1 Haddadi, Minna A1 Benes, Judith A1 Jones, Richard S. YR 2020 UL http://www.genetics.org/content/214/3/623.abstract AB Polycomb-group (PcG) proteins are evolutionarily conserved epigenetic regulators whose primary function is to maintain the transcriptional repression of target genes. Recruitment of Drosophila melanogaster PcG proteins to target genes requires the presence of one or more Polycomb Response Elements (PREs). The functions or necessity for more than one PRE at a gene are not clear and individual PREs at some loci may have distinct regulatory roles. Various combinations of sequence-specific DNA-binding proteins are present at a given PRE, but only Pleiohomeotic (Pho) is present at all strong PREs. The giant (gt) locus has two PREs, a proximal PRE1 and a distal PRE2. During early embryonic development, Pho binds to PRE1 ∼30-min prior to stable binding to PRE2. This observation indicated a possible dependence of PRE2 on PRE1 for PcG recruitment; however, we find here that PRE2 recruits PcG proteins and maintains transcriptional repression independently of Pho binding to PRE1. Pho-like (Phol) is partially redundant with Pho during larval development and binds to the same DNA sequences in vitro. Although binding of Pho to PRE1 is dependent on the presence of consensus Pho-Phol-binding sites, Phol binding is less so and appears to play a minimal role in recruiting other PcG proteins to gt. Another PRE-binding protein, Sp1/Kruppel-like factor, is dependent on the presence of Pho for PRE1 binding. Further, we show that, in addition to silencing gene expression, PcG proteins dampen transcription of an active gene.