Epigenetic and transcription factors control specific gene transcription profiles that instruct cells to proliferate and differentiate throughout development. Underlying this process the chromatin structure is dynamically shaped by different enzymatic complexes called chromatin remodelers. Among them, the C. elegans Mi2 homolog LET-418/Mi2 is required for post-embryonic development and ensures that the germline-specific transcriptional program is silent in somatic cells. By performing a genome-wide RNAi screen, we identified a
let-418 genetic interactor,
lsl-1, which encodes a close homolog of the human ZFP57 zinc-finger transcription factor involved in imprinting. LSL-1 is a germ cell specific protein, whose expression is first observed in the P4 blastomere and maintained in the germ cells through adulthood. Absence of LSL-1 activity leads to various defects. Germline nuclei do not progress normally through meiotic prophase and aberrant chromatin organization and nuclear morphology is observed during homologous chromosome pairing in
lsl-1 mutants. Furthermore, an increased level of apoptosis, that relies on pairing and DNA damage checkpoints, is indicative of a high level of genome instability. By analysing the transcriptome of LSL-1 together with the ChIP-seq data available from the modERN (ENCODE) resource, we found out that LSL-1 is acting as a transcriptional activator of germline genes which are involved in different aspects of germline development, including meiotic chromosomes pairing and genome stability. Finally, we show that these defects are partially dependent on the chromatin proteins LET-418/Mi2 and HPL-2/HP1. We propose a model where the transcription factor LSL-1 is antagonizing repressive chromatin formation by LET-481/Mi2 and/or HPL-2/HP1 at germline gene promoters to allow expression of the proper gene repertoire for gamete production. In the other hand, absence of LSL-1 from somatic cells ensures that germline genes remain silent. Further molecular analysis of this interaction will let us know how LSL-1 is modifying chromatin accessibility to allow transcription.