The Upstream Sequence Transcription Complex dictates nucleosome positioning and promoter accessibility at piRNA genes in the C. elegans germ line.

The piRNA pathway is a conserved germline-specific small RNA pathway that ensures genomic integrity and continued fertility. In C. elegans and other nematodes, Type-I piRNAs are expressed from >10,000 independently transcribed genes clustered within two discrete domains of 1.5 and 3.5 MB on Chromosome IV. Clustering of piRNA genes contributes to their germline-specific expression, but the underlying mechanisms are unclear. We analyze isolated germ nuclei to demonstrate that the piRNA genomic domains are located in a heterochromatin-like environment. USTC (Upstream Sequence Transcription Complex) promotes strong association of nucleosomes throughout piRNA clusters, yet organizes the local nucleosome environment to direct the exposure of individual piRNA genes. Localization of USTC to the piRNA domains depends upon the ATPase chromatin remodeler ISW-1, which maintains high nucleosome density across piRNA clusters and ongoing production of piRNA precursors. Overall, this work provides insight into how chromatin states coordinate transcriptional regulation over large genomic domains, with implications for global genome organization. Author summary: Here we address how gene expression is coordinated over long stretches of DNA that is embedded in a dense chromatin environment. We focus on a large DNA domain that contains thousands of tiny noncoding piRNA genes that are only expressed in germ cells. Our work demonstrates that a specific factor called USTC works with chromatin remodeling factors and with the core transcription complex to activate piRNA gene expression. The ISW-1 chromatin remodeler creates a dense environment that is favorable for USTC to be recruited to piRNA genes. USTC then clears the chromatin away from a space around each piRNA gene that allows for the factor TBP-1 to bind and presumably recruit the core transcriptional machinery to turn on the short piRNA. This work illuminates a mechanism by which both local and long-distance regulatory information can be integrated to coordinate gene expression. [ABSTRACT FROM AUTHOR]