Poster abstracts

Poster number 39 submitted by Yi-Hui Wang

An AT-hook transcription factor promotes transcription of piRNA, histone and spliced-leader gene clusters

Yi-Hui Wang (Ohio State Biochemistry Program, The Ohio State University), Hannah L. Hertz (Department of Biological Chemistry and Pharmacology; The Center for RNA Biology), Benjamin Pastore (Department of Biological Chemistry and Pharmacology; The Center for RNA Biology), Wen Tang (Department of Biological Chemistry and Pharmacology; The Center for RNA Biology)

Abstract:
PIWI-interacting RNAs (piRNAs) are a class of small non-coding RNAs with 21-35 nucleotides(nts) in length. These molecules are crucial for silencing transposable elements to maintain germline integrity. In C. elegans, piRNAs originate from 15,000 discrete transcriptional units within piRNA clusters. The promoter regions of these piRNA genes contain a Ruby motif, flanked by upstream and downstream AT-rich motifs. The Ruby motif is known to play an essential role in facilitating the binding of the upstream sequence transcription complex (USTC), including TOFU-5, TOFU-4, SNPC-4, and PRDE-1, thereby promoting piRNA transcription. While the functional importance of the Ruby motif is widely recognized, the role of the AT-rich sequences in piRNA transcription remains unclear. During gene expression, AT-rich motifs are known to modulate DNA structure and accessibility, facilitating the formation of protein-DNA complexes involved in transcriptional regulation. In this study, we identified a member of the AT-hook family, ATTF-6, as a key factor involved in binding to the AT-rich motif and contributing to piRNA production. We observed that GFP tagged ATTF-6 forms foci at piRNA gene clusters, and these foci are co-dependent with USTC. Interestingly, through chromatin immunoprecipitation followed by sequencing (ChIP-Seq), we found that ATTF-6 not only binds to piRNA promoters but also to the promoters of histone gene clusters and rDNA-spliced-leader (SL) clusters. Loss of ATTF-6 leads to a depletion in histone production, SL transcription, and piRNA precursors. This study provides novel insights into the ability of a single transcription factor to engage in different gene transcriptional pathways, highlighting its involvement in their transcriptional regulation and production.

Keywords: piRNA biogenesis, AT-hook transcription factor