Biology subjects

Brockett, J. S.

Publications and source records attributed to Brockett, J. S..

3 recordsLinked to original sources

bioRxiv2025

The Dream and MEC NuRD Complexes reinforce SPR-5/MET-2 maternal reprogramming to maintain the germline-soma distinction

The proper coordination of transcription factors, ATP dependent chromatin remodelers and histone modifications is essential for tissue specific gene expression, but how gene expression is regulated at these different levels is not well understood. In C. elegans, H3K4 methylation that is acquired in the germline is reprorgammed at fertilization by the H3K4me1/2 demethlyase SPR-5/LSD1/KDM1A and the H3K9 methyltransferase MET-2/SETDB1/KMT2E. SPR-5/MET-2 maternal reprogramming is required to help establish the germline-soma distinction and prevent developmental delay by preventing inherited H3K4 methylation from inappropriately maintaining germline gene expression in somatic tissues. To determine if the DREAM transcriptional repressor complex and the MEC NuRD ATP dependent nucleosome remodeling and histone deacetylase complex function to reinforce SPR-5/MET-2 maternal reprogamming, we asked if loss of these complexes affects the ectopic germline transcription and developmental delay in spr-5; met-2 double mutants. We find that knocking down the DREAM or MEC NuRD complexes specifically exacerbates the developmental delay and ectopic expression of germline genes in the soma caused by loss of SPR-5 and MET-2. In addition, the DREAM and MEC NuRD complexes bind together at SPR-5/MET-2 reprogramming targets. These data suggest that the transcriptional repression of DREAM and the ATP dependent chromatin remodeling and deactylation activities of the MEC NuRD complex are required somatically to reinforce maternal histone reporgamming by SPR-5/MET-2. Thus, these data provide a novel example of how gene regulation is coordinated at multiple levels to maintain the germline-soma distinction and ensure proper development.

genetics↗

bioRxiv2024

Centrocortin potentiates co-translational localization of its mRNA to the centrosome via dynein

Centrosomes rely upon proteins within the pericentriolar material to nucleate and organize microtubules. Several mRNAs also reside at centrosomes, although less is known about how and why they accumulate there. We previously showed that local Centrocortin (Cen) mRNA supports centrosome separation, microtubule organization, and viability in Drosophila embryos. Here, using Cen mRNA as a model, we examine mechanisms of centrosomal mRNA localization. We find that while the Cen N-terminus is sufficient for protein enrichment at centrosomes, multiple domains cooperate to concentrate Cen mRNA at this location. We further identify an N-terminal motif within Cen that is conserved among dynein cargo adaptor proteins and test its contribution to RNA localization. Our results support a model whereby Cen protein enables the accumulation of its own mRNA to centrosomes through a mechanism requiring active translation, microtubules, and the dynein motor complex. Taken together, our data uncover the basis of translation-dependent localization of a centrosomal RNA required for mitotic integrity. SummaryEnrichment of Centrocortin (Cen) mRNA at centrosomes is required for mitotic fidelity. This study describes a mechanism underlying co-translational Cen mRNA targeting involving microtubules, the dynein motor, and a highly conserved dynein binding motif within the Cen coding sequence.

cell biology↗

bioRxiv2020

Failure to maternally reprogram histone methylation causes developmental delay due to germline transcription in somatic tissues

Embryos undergo extensive reprogramming at fertilization to prevent the inappropriate inheritance of histone methylation. In C. elegans, this reprogramming is mediated by the H3K4me2 demethylase, SPR-5, and the H3K9 methyltransferase, MET-2. In contrast to this reprogramming, the H3K36 methyltransferase, MES-4, maintains H3K36me2/3 at germline genes between generations to help re-establish the germline. To determine whether the MES-4 germline inheritance system antagonizes spr-5; met-2 reprogramming, we examined the interaction between these two systems. We find that the developmental delay of spr-5; met-2 mutant progeny is associated with ectopic H3K36me2/3 and the ectopic expression of MES-4 targeted germline genes in somatic tissues. Furthermore, the developmental delay is dependent upon MES-4 and the H3K4 methyltransferase, SET-2. We propose that the MES-4 inheritance system prevents critical germline genes from being repressed by maternal spr-5; met-2 reprogramming. Thus, the balance of inherited histone modifications is necessary to distinguish germline versus soma and prevent developmental delay.

developmental biology↗