A germline PAF1 paralog complex ensures cell type-specific gene expression

ABSTRACT Animal germline development and fertility rely 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 relies on testis-specific paralogs of canonical Polymerase Associated Factor 1 Complex (PAF1C) proteins, which form a testis-specific PAF1C (tPAF). Consequently, tPAF mutants cause aberrant expression of hundreds of downstream genes due to read-in transcription. Furthermore, tPAF facilitates expression of Y-linked male fertility factor genes, and thus broadly maintains spermatocyte-specific gene expression. Consistently, tPAF is required for the segregation of meiotic chromosomes and male fertility. Supported by comparative in vivo protein interaction assays, we provide a mechanistic model for the functional divergence of tPAF and PAF1C and for transcription termination as a developmentally regulated process required for cell type-specific gene expression.