PATCs across the C. elegans genome

Periodic A_n/T_n 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 periodic clusters of A or T nucleotides spaced by 10 bp and extends over relatively long distances (hundreds to thousands of base pairs). For this reason, the structure was named Periodic A_n/T_n 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 strongly enriched on autosome arms, which are also enriched for repressive chromatin modifications and transposable elements (Liu et al., 2010). However, on 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 can partially prevent (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; we could not detect enhanced somatic expression. Other laboratories have 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 PATCs alleviated the silencing of endogenous genes tagged by CRISPR.

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 overview of pre-calculated PATC values for all C. elegans protein-coding genes.
A genome browser with a continuous track of PATCs values.
An online analysis 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.

Download the PATC algorithm

Software

PATC 2006 for mac

PATC 2006 for linux

PATC 2016 for mac (balanced option)

PATC 2016 for linux (balanced option)

PATC Source files

Data Files

PATC algorithm documentation (Fire et al., 2006)

Pre-calculated PATC Genomic trace for C. elegans ce11/WS245 (Frøkjær-Jensen et al., 2016)

The app

This website is generated via custom modified css/html code running in R via the shiny library. Different public available shiny apps from the R-studio shiny gallery were source of inspiration in the development of this app.
The genome browser is produced via a custom modified script based on igv.js.
All the templates, libraries, and programs used to produce this site are under the MIT and GNU licenses.

The PATC algorithm

Andrew Fire et al. (2006) developed the original PATC algorithm. This server uses a modified "balanced" PATC algorithm (Frøkjær-Jensen et al., 2016). This app acts as a front-end for the balanced alogirhtm which runs in the background.

The Laboratory of Synthetic Genome Biology

The Laboratory of Synthetic Genome Biology is located in building 2 - level 3 (Ibn Al-Haytham – Above Spine) at King Abdullah University of Science and Technology (KAUST).
Contact info:
Christian-Froekjaer Jensen, Ph.D.
Assistant Professor of Bioscience
Laboratory of Synthetic Genome Biology
Email: cfjensen@kaust.edu.sa

The people behind the app

The app was originally conceived by Christian Frøkjær-Jensen and implemented by Amhed Missael Vargas Velazquez. Furthermore, the PATC app is on the web thanks to Amazon Web Services (AWS) and the original efforts of the Linux and Advanced Platforms team in KAUST.