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SIN3 acts in distinct complexes to regulate the germline transcriptional program in C. elegans [sin-3(tm1276)]

ABSTRACT: SIN3 acts in distinct complexes to regulate the germline transcriptional program in C. elegans [sin-3(tm1276)]

PROVIDER: PRJNA945400 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23881370.fastq.gz	Fastqsanger.gz
	SRR23881371.fastq.gz	Fastqsanger.gz
	SRR23881372.fastq.gz	Fastqsanger.gz
	SRR23881373.fastq.gz	Fastqsanger.gz
	SRR23881374.fastq.gz	Fastqsanger.gz

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SIN3 acts in distinct complexes to regulate the germline transcriptional program in C. elegans [sin-3(tm1276)]

Project description:The SIN3 transcriptional coregulator influences gene expression through multiple interactions that include histone deacetylases (HDACs). Haploinsufficiency and mutations in SIN3 are the underlying cause of Witteveen-Kolk syndrome and related intellectual disability (ID)/autism syndromes, emphasizing its key role in development. However, little is know on its complexity of interactions and functions in developmental processes. Here we show that loss of SIN-3, the single SIN3 homologue in Caenorhabditis elegans, results in maternal effect sterility associated with deregulation of the germline transcriptome, including derepression of X-linked genes. Using proteomics analysis we identify at least two SIN3 complexes containing distinct HDACs and differentially contributing to fertility. Single cell smFISH reveals that loss of sin-3 stochastically derepresses X linked genes in individual germ cells. We further identify acetylation marks whose abundance depends on SIN3. Together, this work provides a powerful paradigm for the in vivo study of SIN3 and associated proteins.

2023-10-04 | GSE227498 | GEO

SIN3 acts in distinct complexes to regulate the germline transcriptional program in C. elegans [sin-3(syb2172) and hda-3(ok1991)]

2023-10-04 | GSE227368 | GEO

SIN3 acts in distinct complexes to regulate the germline transcriptional program in C. elegans [sin-3(syb2172) and hda-3(ok1991)]

Project description:SIN3 acts in distinct complexes to regulate the germline transcriptional program in C. elegans [sin-3(syb2172) and hda-3(ok1991)]

| PRJNA944713 | ENA

SIN3 acts in distinct complexes to regulate the germline transcriptional program in C. elegans

Project description:SIN3 acts in distinct complexes to regulate the germline transcriptional program in C. elegans

| PRJNA945391 | ENA

MS-based proteomic characterization of SIN3-containing complexes in C. elegans

2023-10-02 | PXD039853 | Pride

SIN-3 transcriptional coregulator maintains mitochondrial homeostasis and polyamine flux

Project description:Mitochondrial function relies on the coordinated transcription of mitochondrial and nuclear genomes to assemble respiratory chain complexes. Across species, the SIN3 coregulator influences mitochondrial functions, but how its loss impacts mitochondrial homeostasis and metabolism in the context of a whole organism is unknown. Exploring this link is important because SIN3 haploinsufficiency causes intellectual disability/autism syndromes and SIN3 plays an important role in tumor biology. Here we show that loss of C. elegans SIN-3 results in transcriptional deregulation of mitochondrial- and nuclear-encoded mitochondrial genes, potentially leading to mito-nuclear imbalance. Consistent with impaired mitochondrial function, sin-3 mutants show extensive mitochondrial fragmentation by transmission electron microscopy (TEM) and in vivo imaging, and altered oxygen consumption. Metabolomic analysis of sin-3 mutant animals identifies a signature of mitochondria stress and deregulation of methionine flux, resulting in decreased S-adenosyl methionine (SAM) and increased polyamine levels. Our results identify SIN3 as a key regulator of mitochondrial dynamics and metabolic flux, with important implications for human pathologies.

2024-04-01 | MTBLS8439 | MetaboLights

A role for mammalian Sin3 in permanent gene silencing

Project description:The multi-subunit Sin3 co-repressor complex regulates gene transcription through deacetylation of nucleosomes. However, the full range of Sin3 activities and targets is not well understood. Here, we have investigated genome-wide binding of mouse Sin3 and RBP2 as well as histone modifications and nucleosome positioning as a function of myogenic differentiation. Remarkably, we find that Sin3 complexes spread immediately downstream of the transcription start site on repressed and transcribed genes during differentiation. We show that RBP2 is part of a Sin3 complex, and on a subset of E2F4 target genes, the coordinated activity of Sin3 and RBP2 leads to deacetylation, demethylation, and repositioning of nucleosomes. Our work provides evidence for coordinated binding of Sin3, chromatin modifications, and chromatin remodeling within discrete regulatory regions, suggesting a model in which spreading of Sin3 binding is ultimately linked to permanent gene silencing on a subset of E2F4 target genes.

2008-11-06 | GSE13247 | GEO

Physical and functional interaction between the SET1 complex component CFP-1/CXXC and the Sin-3S/HDAC complex in C. elegans embryos

Project description:The highly conserved CFP1 CXXC zinc finger protein targets SET1 family complexes to promoter regions to implement methylation of histone H3 Ly4 (H3K4me), a mark that correlates with gene expression depending on the chromatin context. Whether CFP1 physically interacts with additional chromatin modifying proteins on chromatin has not been investigated. By applying interaction proteomics coupled to mass spectrometry to identify factors that interact with C. elegans CFP-1, we establish a link between CFP-1 and the Rpd3/Sin3 histone deacetylase (HDAC) small complex (Rpd3/Sin3S) in embryos. We show that CFP-1 directly interacts with SIN-3 through a highly conserved C-terminal domain, and that the two proteins extensively colocalize with H3K4me3 at promoter regions genome-wide. Animals lacking sin-3, cfp-1 or the catalytic H3K4 methyltransferase subunit set-2/SET1 show misregulation of common genes in early embryos, reduction in fertility, and defects in the division of intestinal cells in adults, consistent with common developmental functions. Our results suggest that in addition to its well characterized role as a central subunit of the SET-2/SET1 complex, CFP-1 interacts with the Sin3S/HDAC complex at promoter regions to influence gene expression in a developmental context. This has implications for the coordinate regulation of gene expression by chromatin associated complexes with distinct activities.

2019-09-26 | GSE110072 | GEO

Physical and functional interaction between the SET1/COMPASS complex component CFP-1/CXXC and a Sin3S HDAC complex

Project description:The CFP1/CXXC protein targets SET1/COMPASS complexes to non-methylated CpG rich promoter regions to implement tri-methylation of histone H3 Ly4 (H3K4me3). Although H3K4me3 is widely associated with gene expression, the effects of CFP1 loss depend on chromatin context. Little is known about how CFP1 binding is coordinated with other chromatin factors. Using a proteomics approach, we establish a link between C. elegans CFP1 and a small Rpd3/Sin3 histone deacetylase (HDAC) complex (Sin3S). Mutants of CFP-1, SIN-3, and the catalytic subunit SET-2/SET1 have similar phenotypes and misregulate the expression of common genes. CFP-1 directly interacts with SIN-3 through a region including the conserved PAH1 domain, and contributes to recruitment of SIN-3 and the Sin3S subunit HDA-1 to H3K4me3 enriched promoters. Our results reveal a novel role for CFP-1 in mediating interaction between SET1/COMPASS and a Sin3 HDAC small complex at promoters, with implications for the coordinate regulation of gene expression by chromatin- associated complexes with distinct activities.

2019-09-29 | GSE114715 | GEO

SIN3 acts in distinct complexes to regulate the germline transcriptional program in C. elegans

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-10-04 | GSE227499 | GEO