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. 2020 Sep 22;8:561791. doi: 10.3389/fcell.2020.561791

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Copyright © 2020 Robert, Knutson, Rechtsteiner, Garvis, Yvert, Strome and Palladino.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Chromosome X desilencing is a priming event for loss of germline identity. In (A,C–F) *p-value < 0.05 and ***p-value < 0.001 calculated by hypergeometric test. Color code in bar graphs is the same throughout. (A) Chromosome distribution of contributors. p = 4.4e-5 and 6.1e-193 for distribution of down- and upregulated contributors, respectively. (B) Distribution of WCA score according to location of the genes on autosomes or the X chromosome (pve = percent of variance explained by PC1 when within-class PCA is run on the indicated set of genes only). (C) Comparison of upregulated contributors with mes-2; mes-4 up- and downregulated genes and chromosome distribution of upregulated class. p = 2.34e-97 for over-enrichment in mes-2; mes-4 upregulated genes, p = 3.6e-4 for under-enrichment in mes-2; mes-4 downregulated genes, p = 3.2e-21 for chromosome distribution. (D) Comparison of downregulated contributors with mes-2; mes-4 up- and down-regulated genes and chromosome distribution of downregulated class. p = 3.9e-5 for under-enrichment in mes-2; mes-4 upregulated genes, p = 5.84e-14 for over-enrichment in mes-2; mes-4 downregulated genes, p = 0.5 for chromosome distribution. (E) Comparison of upregulated contributors with genes activated by GLP-1. p = 1.25e-24 for over-enrichment in GLP-1 activated genes, p = 7e-6 for over-enrichment in X-linked GLP-1 activated genes, p = 1e-2 for over-enrichment in X-linked GLP-1 activated genes repressed by PRC2/MES-4. (F) Comparison of upregulated contributors with genes activated by LIN-15B. Color code is the same as in (A). p = 7.7e-9 for over-enrichment in X-linked LIN-15B-activated genes, p = 8e-3 for over-enrichment in X-linked LIN-15B-activated genes repressed by PRC2/MES-4. (G) Comparison of X-linked upregulated contributors with genes repressed by PRC2/MES-4 and genes activated by GLP-1/NOTCH or LIN-15B. Summary of connections between the regulatory networks that regulate various classes of X-linked genes in set-2 mutant germlines.