Poster abstracts

Poster number 143 submitted by Chin Wang

Investigating AT-hook Proteins and Their Role in PATC-Mediated Gene Regulation in C. elegans

Chin Wang (Department of Biological Chemistry and Pharmacology, Molecular, Cellular and Developmental Biology Program), Yi-Hui Wang (Department of Biological Chemistry and Pharmacology, Center for RNA Biology, Ohio State Biochemistry Program), Hannah L. Hertz (Department of Biological Chemistry and Pharmacology), Wen Tang (Department of Biological Chemistry and Pharmacology, Center for RNA Biology, Ohio State Biochemistry Program, Molecular, Cellular and Developmental Biology Program)

Abstract:
The animal germ line produces gametes that transmit genetic and epigenetic information from generation to generation. Organisms have evolved an array of specialized pathways to ensure proper gene expression. One such regulatory element in C. elegans is the periodic An/Tn-cluster (PATC), which features a 10-base pair periodicity and has been implicated in promoting the expression of both transgenes and endogenous genes (Fire et al., 2006, Aljohani et al., 2020, Seroussi et al., 2022). However, the mechanisms how PATCs regulate gene expression remain poorly understood. Our unpublished data suggest that AT-hook proteins, known to bind to AT-rich motifs, may play a role. We hypothesize that AT-hook proteins interact with PATC sequences to promote gene expression. To test this, we conducted a RNAi based screen targeting individual members of the AT-hook family in C. elegans strains expressing a GFP reporter with PATCs (Frøkjær-Jensen et al., 2016). Among the nine AT-hook genes tested, knockdown of two resulted in GFP silencing specifically in the germ line. Our ongoing experiments, including ChIP-seq and transcriptome profiling, aim to elucidate the mechanisms by which AT-hook proteins interact with PATCs and regulate gene expression in the germ line.

References:
1. Fire, A., Alcazar, R., and Tan, F. (2006). Unusual DNA structures associated with germline genetic activity in Caenorhabditis elegans. Genetics 173, 1259–1273.
2. Aljohani, M.D., El Mouridi, S., Priyadarshini, M., et al. (2020). Engineering rules that minimize germline silencing of transgenes in simple extrachromosomal arrays in C. elegans. Nat. Commun. 11, 6300.
3. Seroussi, U., Li, C., Sundby, A.E., Lee, T.L., Claycomb, J.M., and Saltzman, A.L. (2022). Mechanisms of epigenetic regulation by C. elegans nuclear RNA interference pathways. Semin. Cell Dev. Biol. 127, 142–154.
4. Frøkjær-Jensen, C., Jain, N., Hansen, L., Davis, M.W., Li, Y., Zhao, D., Rebora, K., Millet, J.R.M., Liu, X., Kim, S.K., Dupuy, D., Jorgensen, E.M., and Fire, A.Z. (2016). An abundant class of non-coding DNA can prevent stochastic gene silencing in the C. elegans germline. Cell 166, 343–357.

Keywords: AT-hook, PATCs (Periodic AnTn Clusters), Gene expression regulation