Rappaport, Y. | Search bioRxiv

bioRxiv2023

LincRNAs enable germ cells differentiation by promoting PUF proteins condensation

Successful tissue homeostasis depends on a balance between proliferation and differentiation. Two PUF proteins, FBF-1 and FBF-2, maintain stem-cells proliferation in C. elegans germ-cells by binding and destabilizing transcripts which promote meiotic entry. However, it is unclear how meiosis initiates because the FBF are also present at significant levels in late proliferative and early meiotic cells. We found that the three long-intergenic-non-coding RNAs (lincRNAs) that bind the FBF proteins promote timely meiotic entry. Deletion of the lincRNA genes leads to additive reduction in progenitor cell number and fertility. In the lincRNAs deletion mutant, expression of many known FBF-2 targets is significantly lower, suggesting over-activation of FBF-2. In this mutant, FBF-2 localization in perinuclear condensates is reduced, and its cytoplasmic fraction increases. Moreover, FBF-2 association with the germline P-granules decreases without the lincRNAs. Our results indicate that lincRNAs act to promote meiotic differentiation by spatially restricting pro-proliferation factors into phase-separated granules.

developmental biology↗

bioRxiv2020

Chromosome Integrity is Required for the Initiation of Meiotic Sex Chromosome Inactivation in Caenorhabditis elegans

During meiosis of heterogametic cells, such as XY meiocytes, sex chromosomes of many species undergo transcriptional silencing known as meiotic sex chromosome inactivation (MSCI). Silencing also occurs in aberrantly unsynapsed autosomal chromatin. The silencing of unsynapsed chromatin, is assumed to be the underline mechanism for MSCI. Initiation of MSCI is disrupted in meiocytes with sex chromosome-autosome translocations. Whether this is due to aberrant synapsis or the lack of sex chromosome integrity has never been determined. To address this, we used CRISPR to engineer Caenorhabditis elegans stable strains with broken X chromosomes that didnt undergo translocations with autosomes. In early meiotic nuclei of these mutants, the X fragments lack silent chromatin modifications and instead the fragments are enriched with transcribing chromatin modifications. Moreover, the level of active RNA polymerase II staining on the X fragments in mutant nuclei is similar to that on autosomes, indicating active transcription on the X. Contrary to previous models, which predicted that any unsynapsed chromatin is silenced during meiosis, X fragments that did not synapse were robustly stained with RNA polymerase II and gene expression levels were high throughout the broken X. Therefore, lack of synapsis does not trigger MSCI if sex chromosome integrity is lost. Moreover, our results suggest that a unique character of the chromatin of sex chromosomes underlies their lack of meiotic silencing due to both unsynapsed chromatin and sex chromosome mechanisms when their integrity is lost.

cell biology↗