Periodic An/Tn Clusters (PATCs)
Fire et al. (2006) first identified an unusual non-coding DNA structure that was associated with genes expressed in the germline of C. elegans. The unusual DNA structure consists of an enrichment of An or Tn clusters with 10 bp spacing that extends over relatively long distances (hundreds to thousands of base pairs). For this reason, the structure was named Periodic An/Tn Clusters (PATCs) (Fire et al., 2006). PATCs are strongly associated with genes that are expressed in the germline and, when present, are strongly enriched in non-coding regions (5', intronic, and 3'). At a genome-scale, PATCs are heavily enriched on autosome arms, which are also enriched for repressive chromatin modifications and transposable elements (Liu et al., 2010). However, at a local scale, PATCs are anti-correlated with repressive histone marks (Gu and Fire, 2010) which suggests that PATCs may confer resistance to repressive chromatin.
Functionally, PATCs were shown to play a role in preventing (trans)gene silencing in the germline of C. elegans. We showed that single-copy fluorescent transgenes containing PATC-rich sequences in introns were resistant to positional silencing in repressive genomic domains ("arms") and stochastic silencing in euchromatic domains ("centers") (Frøkjær-Jensen et al., 2016). The effect appeared to be specific to germline expression; no enhanced somatic expression was detected. Several other laboratories have also shown that transgenes engineered to contain PATCs are resistant to silencing in different contexts: Zhang et al. (2018) showed that PATC-rich transgenes were resistant to small RNA-mediated silencing via the piRNA pathway. Fielmich et al. (2018) demonstrated that silencing of endogenous genes tagged by CRISPR was alleviated by including PATCs.
At present, we have very little understanding of how PATCs influence (trans)gene silencing but a working model is that PATCs constrain DNA
and nucleosome interactions to resist the assembly of higher-order heterochromatic structures (Fire et al., 2006).
Here we have developed a set of tools based on the original PATC algorithm (Fire et al., 2006)
to enhance the study of PATCs in C. elegans and other organisms: An interactive view of pre-calculated PATC values for
all C. elegans protein-coding genes and a web service that calculates the PATC value of arbitrary DNA sequences.
References
Fire, A., Alcazar, R., and Tan, F. (2006). Unusual DNA structures associated with germline genetic activity in Caenorhabditis elegans. Genetics 173, 1259–1273.
Gu, S.G., and Fire, A. (2010). Partitioning the C. elegans genome by nucleosome modification, occupancy, and positioning. Chromosoma 119, 73–87.
Liu, T., Rechtsteiner, A., Egelhofer, T.A., Vielle, A., Latorre, I., Cheung, M.-S., Ercan, S., Ikegami, K., Jensen, M., Kolasinska-Zwierz, P., et al. (2010). Broad chromosomal domains of histone modification patterns in C. elegans. Genome Res.
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., et al. (2016). An Abundant Class of Non-coding DNA Can Prevent Stochastic Gene Silencing in the C. elegans Germline. Cell 166, 343–357.
Fielmich, L.-E., Schmidt, R., Dickinson, D.J., Goldstein, B., Akhmanova, A., and van den Heuvel, S. (2018). Optogenetic dissection of mitotic spindle positioning in vivo. ELife 7, e38198.
Zhang, D., Tu, S., Stubna, M., Wu, W.-S., Huang, W.-C., Weng, Z., and Lee, H.-C. (2018). The piRNA targeting rules and the resistance to piRNA silencing in endogenous genes. Science 359, 587–592.