XOL-1 regulates developmental timing by modulating the H3K9 landscape in C. elegans early embryos

Abstract

Sex determination in the nematode C. elegans is controlled by the master regulator XOL-1 during embryogenesis. Expression of xol-1 is dependent on the ratio of X chromosomes and autosomes, which differs between XX hermaphrodites and XO males. In males, xol-1 is highly expressed and in hermaphrodites, xol-1 is expressed at very low levels. XOL-1 activity is known to be critical for the proper development of C. elegans males, but its low expression was considered to be of minimal importance in the development of hermaphrodite embryos. Our study reveals that XOL-1 plays an important role as a regulator of developmental timing during hermaphrodite embryogenesis. Using a combination of imaging and bioinformatics techniques, we found that hermaphrodite embryos have an accelerated rate of cell division, as well as a more developmentally advanced transcriptional program when xol-1 is lost. Further analyses reveal that XOL-1 is responsible for regulating the timing of initiation of dosage compensation on the X chromosomes, and the appropriate expression of sex-biased transcriptional programs in hermaphrodites. We found that xol-1 mutant embryos overexpress the H3K9 methyltransferase MET-2 and have an altered H3K9me landscape. Some of these effects of the loss of xol-1 gene were reversed by the loss of met-2. These findings demonstrate that XOL-1 plays an important role as a developmental regulator in embryos of both sexes, and that MET-2 acts as a downstream effector of XOL-1 activity in hermaphrodites. Author SummaryVarious organisms have differing ways of determining, at a molecular level, what the sex of a developing embryo is supposed to be. The two sexes in the nematode C. elegans, hermaphrodite and male, have different numbers of X chromosomes. Hermaphrodites have two X chromosomes and males only have one. This mismatch raises an additional problem as hermaphrodites will have twice the amount of genes expressed from the X compared to males. This is solved by a process called dosage compensation, which equalizes gene expression between the sexes. A molecular sensor called XOL-1 detects the number of X chromosomes in an embryo and kick-starts the process of proper sexual development and/or dosage compensation. XOL-1 was known to be very important for activating male development but was believed to not have any role in the development of the hermaphrodite sex. We show that XOL-1 has some crucial roles in hermaphrodite embryos in controlling the rate of development of the embryo, and regulating the timing of dosage compensation. We also show that MET-2, a protein that deposits repressive methyl marks on DNA-bound histone proteins, is involved in this process.