A germline PAF1 paralog complex ensures cell type-specific gene expression (co-IP data)

Animal germline development and fertility relies on paralogs of general transcription factors that recruit RNA polymerase II to ensure cell type-specific gene expression. It remains unclear whether gene expression processes downstream of such paralog-based transcription is distinct from that of canonical RNA polymerase II genes. In Drosophila, the testis-specific TBP-associated factors (tTAFs) activate over a thousand spermatocyte-specific gene promoters to enable meiosis and germ cell differentiation. Here we show that efficient termination of tTAF-activated transcription requires a testis-specific Polymerase Associated Factor 1 Complex (tPAF) composed of paralogs of canonical Polymerase Associated Factor 1 Complex (PAF1C) proteins. Defective transcription termination in tPAF mutants causes aberrant expression of hundreds of downstream genes due to read-in transcription, compromising cell type-specific gene expression in spermatocytes. Consistently, tPAF is required for the segregation of meiotic chromosomes, sperm individualisation, and male fertility. Comparative in vivo proximity labeling assays of tPAF and PAF1C showed tPAF-specific association with tTAF as well as connections to central RNA polymerase II termination factors. Our study uncovers transcription termination as a developmentally regulated process required for cell type-specific gene expression.