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Abstract Dosage compensation inCaenorhabditis elegansequalizes X-linked gene expression between XX hermaphrodites and XO males. The process depends on a condensin- containing dosage compensation complex (DCC), which binds the X chromosomes in hermaphrodites to repress gene expression. Condensin I^DCand an additional five DCC components must be present on the X during early embryogenesis in hermaphrodites to establish dosage compensation. However, whether the DCC’s continued presence is required to maintain the repressed state once established is unknown. Beyond the role of condensin I^DCin X chromosome compaction, additional mechanisms contribute to X- linked gene repression. DPY-21, a non-condensin I^DCDCC component, is an H4K20me2/3 demethylase whose activity enriches the repressive histone mark, H4 lysine 20 monomethylation, on the X chromosomes. In addition, CEC-4 tethers H3K9me3-rich chromosomal regions to the nuclear lamina, which also contributes to X- linked gene repression. To investigate the necessity of condensin I^DCduring the larval and adult stages of hermaphrodites, we used the auxin-inducible degradation system to deplete the condensin I^DCsubunit DPY-27. While DPY-27 depletion in the embryonic stages resulted in lethality, DPY-27 depleted larvae and adults survive. In these DPY-27 depleted strains, condensin I^DCwas no longer associated with the X chromosome, the X became decondensed, and the H4K20me1 mark was gradually lost, leading to X-linked gene derepression. These results suggest that the stable maintenance of dosage compensation requires the continued presence of condensin I^DC. A loss-of-function mutation incec-4, in addition to the depletion of DPY-27 or the genetic mutation ofdpy- 21, led to even more significant increases in X-linked gene expression, suggesting that tethering heterochromatic regions to the nuclear lamina helps stabilize repression mediated by condensin I^DCand H4K20me1. Author SummaryIn some organisms, whether an individual becomes male, female, or hermaphrodite is determined by the number of their sex chromosomes. In the nematodeCaenorhabditis elegans, males have one X chromosome, whereas hermaphrodites have two X chromosomes. This difference in the number of X chromosomes is crucial for deciding whether an individual becomes a hermaphrodite or a male. However, having two X chromosomes can lead to problems because it results in different gene expression levels, resulting in hermaphrodite lethality. To solve this issue, many organisms undergo a process called dosage compensation. Dosage compensation inC. elegansis achieved by a group of proteins known as the dosage compensation complex (DCC), which includes a protein called DPY-27. The function of DPY-27 is essential during early embryonic development. This study shows that in contrast to early embryonic development, larvae and adults can still survive when DPY-27 is missing. In these worms, all known mechanisms involved in dosage compensation are disrupted and the X is no longer repressed. Our results suggest that the maintenance of dosage compensation in nematodes is an active process, and that it is essential for survival when the organism is developing, but once fully developed, the process becomes dispensable. 

Sex determination in the nematodeC.elegansis controlled by the master regulator XOL-1 during embryogenesis. Expression ofxol-1is dependent on the ratio of X chromosomes and autosomes, which differs between XX hermaphrodites and XO males. In males,xol-1is highly expressed and in hermaphrodites,xol-1is expressed at very low levels. XOL-1 activity is known to be critical for the proper development ofC.elegansmales, 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 whenxol-1is 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 thatxol-1mutant embryos overexpress the H3K9 methyltransferase MET-2 and have an altered H3K9me landscape. Some of these effects of the loss ofxol-1gene were reversed by the loss ofmet-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. 

Embryogenesis is characterized by dynamic chromatin remodeling and broad changes in chromosome architecture. These changes in chromatin organization are accompanied by transcriptional changes, which are crucial for the proper development of the embryo. Several independent mechanisms regulate this process of chromatin reorganization, including the segregation of chromatin into heterochromatin and euchromatin, deposition of active and repressive histone modifications, and the formation of 3D chromatin domains such as TADs and LADs. These changes in chromatin structure are directly linked to developmental milestones such as the loss of developmental plasticity and acquisition of terminally differentiated cell identities. In this review, we summarize these processes that underlie this chromatin reorganization and their impact on embryogenesis in the nematode C. elegans.