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A team of heterochromatin factors collaborates with small RNA pathways to combat repetitive elements and germline stress

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Caenorhabditis elegans

PROVIDER: GSE87524 | GEO | 2017/03/11

SECONDARY ACCESSION(S): PRJNA345009

REPOSITORIES: GEO

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A team of heterochromatin factors collaborates with small RNA pathways to combat repetitive elements and germline stress.

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A team of heterochromatin factors collaborates with small RNA pathways to combat repetitive elements and germline stress [RNA-seq]

Project description:Repetitive sequences derived from transposons make up a large fraction of eukaryotic genomes and must be silenced to protect genome integrity. Repetitive elements are often found in heterochromatin; however, the roles and interactions of heterochromatin proteins in repeat regulation are poorly understood. Here we show that a diverse set of C. elegans heterochromatin proteins act together with the piRNA and nuclear RNAi pathways to silence repetitive elements and prevent genotoxic stress in the germ line. Mutants in genes encoding HPL-2/HP1, LIN-13, LIN-61, LET-418/Mi-2, and H3K9me2 histone methyltransferase MET-2/SETDB1 also show functionally redundant sterility, increased germline apoptosis, DNA repair defects, and interactions with small RNA pathways. Remarkably, fertility of heterochromatin mutants could be partially restored by inhibiting cep-1/p53, endogenous meiotic double strand breaks, or the expression of MIRAGE1 DNA transposons. Functional redundancy among these factors and pathways underlies the importance of safeguarding the genome through multiple means.

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A team of heterochromatin factors collaborates with small RNA pathways to combat repetitive elements and germline stress [ChIP-seq]

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Project description:A team of heterochromatin factors collaborates with small RNA pathways to combat repetitive elements and germline stress

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Diverse Heterochromatin-Associated Proteins Repress Distinct Classes of Genes and Repetitive Elements

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

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Diverse Heterochromatin-Associated Proteins Repress Distinct Classes of Genes and Repetitive Elements (srHC-seq)

Project description:Heterochromatin, typically marked by H3K9me3 or H3K27me3, is key to the repression of genes and repetitive elements. The mechanisms responsible for establishing and maintaining heterochromatin in a locus specific manner are unclear. Heterochromatin restricts cell identity by preventing activation of alternative lineage genes. This barrier can be partially overcome by inducing ectopic transcription factors (TFs) to activate an alternative transcriptional program. However, TFs are impeded by highly restrictive heterochromatin leading to low reprogramming rates and incomplete activation of the target transcriptome. Previously we utilized the heterochromatin property of sonication resistance to identify 172 proteins associated with sonication resistant heterochromatin (srHC) by mass spectrometry (Becker, et al., 2017). We hypothesized that by functionally assessing the srHC proteins and identifying the genes they repress during reprogramming we could improve our understanding of heterochromatin maintenance and learn how to disrupt heterochromatin to enhance reprogramming. Focusing on reprogramming from fibroblasts to induced human hepatocytes (hiHeps) we conducted an siRNA screen of 97 srHC proteins without reprogramming factors (noTF) and with hiHep reprogramming and assessed the impact on the expression of genes located in srHC domains by RNA-seq. We identified enhancer of rudimentary homolog (ERH) as a key regulator of H3K9me3 heterochromatin maintenance. ERH was found to associate broadly with H3K9me3 domains and when depleted caused global changes in H3K9me3 and srHC. Collectively our screen of srHC protein repressive function demonstrates specific functionality of groups of srHC proteins and increases our understanding of H3K9me3 gene repression.

2021-06-24 | GSE154232 | GEO

Diverse Heterochromatin-Associated Proteins Repress Distinct Classes of Genes and Repetitive Elements (ChIP-seq)

2021-06-24 | GSE154214 | GEO

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