Biology subjects

Wicky, C.

Publications and source records attributed to Wicky, C..

4 recordsLinked to original sources

bioRxiv2026

The transcription factor LSL-1 interacts with the chromatin factors HIM-17, XND-1 and BRA-2 to promote the germline-specific transcriptional repertoire and to safeguard germ cell fate in C. elegans

Germ cells are the only cells of an organism that pass onto the next generation and, hence perpetuate the species. To ensure this, germ cells need dedicated transcriptional repertoire, that ensure specification, proliferation, differentiation and fate maintenance. We previously characterized LSL-1, a conserved zinc-finger transcription factor that acts as a major direct transcriptional activator of genes involved in germ cell development, fate specification, meiosis and genome stability. Here, we show that LSL-1 interacts with the transcription factor HIM-17, the chromatin proteins BRA-2 and XND-1. These proteins are functionally related to LSL-1 and they colocalize at germline gene promoters, forming most likely a transcription-promoting complex. Furthermore, LSL-1 lies in close proximity to members of the COMPASS and the MOF complexes, corroborating the observation that HIM-17 and LSL-1 are required to maintain normal level of H3K4 methylation in the gonad. Finally, we show that LSL-1 interacting partners are necessary to maintain germ cell fate. Altogether, we propose that LSL-1 interacts with transcription regulators and chromatin modifiers to ensure the establishment of the transcriptional repertoire appropriate for germline function as well as for cell fate maintenance.

biochemistry↗

bioRxiv2025

The chromatin remodeler LET-418/Mi-2 regulates the intracellular pathogen response in the C. elegans intestine

Chromatin remodeling provides essential transcriptional regulation for all biological processes. In Caenorhabditis elegans, the chromatin remodeler LET-418, a homolog of the human Mi-2{beta} protein, plays a critical role in regulating development, organogenesis, tissue maintenance, stress resistance and lifespan. LET-418 is part of several chromatin remodeling complexes and contributes significantly to the balance between growth and defense mechanisms, yet its target genes remain unclear. Using DNA methylation profiling, we identified genomic binding sites and associated target genes of LET-418 and its MEC-complex-specific interactor MEP-1 in the intestine. Consistent with their presence in the same complex, the two proteins shared more than half of their target genes. Functional analysis revealed that LET-418 and MEP-1 target genes are highly active in the intestine and are involved in repressing innate immune responses, including the intracellular pathogen response (IPR). Consistently, in let-418 mutants, IPR-induced genes, such as pals-5 or pals-2 are strongly upregulated, in a manner dependent on ZIP-1, a major transcription factor for IPR. Additionally, we found pathogen levels of the natural intracellular intestinal pathogen Nematocida parisii significantly reduced in let-418 mutants, supporting the observation of increased IPR in this mutant. Altogether, these findings reveal a crucial role for LET-418 as a modulator of the IPR, aligning with its role in maintaining the balance between development and defense.

genomics↗

bioRxiv2024

Birth weight discordance, gene expression, and DNA methylation: A review of epigenetic twin studies

BackgroundBirth weight is considered as an important indicator of environmental conditions during prenatal development. Molecular mechanisms, including epigenetic modifications play an important role in the bodys adaptation to ever changing environmental conditions. As twin design can be used to identify the role of environmental contributions while controlling for genetic variations, numerous monozygotic twin studies have shown how adverse prenatal environment can lead to birth weight discordance (BWD). ObjectiveAn overview of the literature about epigenetic modifications associated with BWD in twins. MethodWe searched PubMed and Ovid MEDLINE(R) databases and included 34 papers that studied associations between BWD and DNA (hydroxy)methylation or gene expression in easily accessible samples of twin pregnancies or peripheral tissues of twins later in life. ResultsResearchers and clinicians still lack consensus on BWD thresholds, which vary between 15-30% depending on the type of placentation and gestational age. The gene expression twin studies measured mostly metabolism-related candidate genes in placental tissues. Only small-scale twin studies measured BWD associated gene expression patterns on genome-wide level using neonatal cells. Most DNA methylation twin studies used epigenome-level analyses, but the analysed tissue and age of sampling varied widely (blood from adults, saliva samples from children, placenta at delivery). Importantly, a handful of growth-related genes (e.g., IGF2, LEPROT, ADRB3, GLUT3) were associated with BWD. ConclusionTranscriptional changes of genes coding for placental glucose transporters and hypoxia-induced proteins possibly reflect compensatory processes in twin pregnancies. Epigenetic regulation of growth-related genes in the offspring offer a relevant mechanism to counterbalance adverse prenatal environment. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=190 HEIGHT=200 SRC="FIGDIR/small/625968v1_ufig1.gif" ALT="Figure 1"> View larger version (78K): org.highwire.dtl.DTLVardef@e20978org.highwire.dtl.DTLVardef@1dbc274org.highwire.dtl.DTLVardef@bb8f40org.highwire.dtl.DTLVardef@1b9cdcc_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical abstract/Figure 1.C_FLOATNO (Created in https://BioRender.com) Although monozygotic twins have almost the same DNA sequence (see double stranded DNA helix in the middle), there are many molecular regulatory processes differentially affected by certain in utero environmental factors (such as unequal blood supply). Therefore, in a proportion of twin pregnancies, the intrauterine growth of the developing embryos is uneven, resulting in substantial birth weight difference. The underlying epigenetic alterations, such as DNA methylation changes can be long-lasting, measurable after birth and may serve as biomarkers reflecting risk for later health problems. An important technical feature is that the DNA molecule is quite stable and the methyl groups are attached covalently (shown as Me), hence methylation analyses are wide-spread in medical studies. C_FIG

genomics↗

bioRxiv2021

The zinc-finger transcription factor LSL-1 is a major regulator of the germline transcriptional program in C. elegans

Specific gene transcriptional programs are required to ensure proper proliferation and differentiation processes underlying the production of specialized cells during development. Gene activity is mainly regulated by the concerted action of transcription factors and chromatin proteins. In the nematode C. elegans, mechanisms that silence improper transcriptional programs in germline and somatic cells have been well studied, however, how are tissue specific sets of genes turned on is less known. LSL-1 is herein defined as a novel crucial transcriptional regulator of germline genes in C. elegans. LSL-1 is first detected in the P4 blastomere and remains present at all stages of germline development, from primordial germ cell proliferation to the end of meiotic prophase. lsl-1 loss-of-function mutants exhibit many defects including meiotic prophase progression delay, a high level of germline apoptosis, and production of almost no functional gametes. Transcriptomic analysis and ChIP-seq data show that LSL-1 binds to promoters and acts as a transcriptional activator of germline genes involved in various processes, including homologous chromosome pairing, recombination, and genome stability. Furthermore, we show that LSL-1 functions by antagonizing the action of the heterochromatin proteins HPL-2/HP1 and LET-418/Mi2 known to be involved in the repression of germline genes in somatic cells. Based on our results, we propose LSL-1 to be a major regulator of the germline transcriptional program during development.

genetics↗