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

Chavez, S. R.; Dozier, J.; Gosrani, S. P.; Nguyen, S. K.; Brockett, J. S.; Blancher, S. D.; Morgan-Benitez, S. L.; Rodriguez, J. D.; Birol, O.; Reeves, M. N.; Schmeichel, K. L.; Katz, D. J.; Carpenter, B. S.

doi:10.1101/2025.07.23.666413

bioRxiv · 10.1101/2025.07.23.666413

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

Chavez, S. R.·Dozier, J.·Gosrani, S. P.·Nguyen, S. K.·Brockett, J. S.·Blancher, S. D.·Morgan-Benitez, S. L.·Rodriguez, J. D.·Birol, O.·Reeves, M. N.·Schmeichel, K. L.·Katz, D. J.·Carpenter, B. S.

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Abstract

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.

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Chavez, S. R., Dozier, J., Gosrani, S. P., Nguyen, S. K., Brockett, J. S., Blancher, S. D., Morgan-Benitez, S. L., Rodriguez, J. D., Birol, O., Reeves, M. N., Schmeichel, K. L., Katz, D. J., Carpenter, B. S.. 2025-07-27. The Dream and MEC NuRD Complexes reinforce SPR-5/MET-2 maternal reprogramming to maintain the germline-soma distinction. https://doi.org/10.1101/2025.07.23.666413

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