Genomic Imprinting and Physiological Processes in Mammals

Tucci, Valter; Isles, Anthony R; Kelsey, Gavin; Ferguson-Smith, Anne C.; Bartolomei, Marisa S.; Benvenisty, Nissim; Bourc’his, Déborah; Charalambous, Marika; Dulac, Catherine; Feil, Robert; Glaser, Juliane; Huelsmann, Lisa; Roshan, John; McNamara, Gráinne; Moorwood, Kim; Muscatelli, Françoise; Sasaki, Hidetada; Strassmann, Beverly I.; Vincenz, Claudius; Wilkins, Jon F.

doi:10.1016/j.cell.2019.01.043

Cited by 426 publications

(398 citation statements)

References 116 publications

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“…Non-DNA-based inheritance could be involved in multiple human disorders (Crews et al, 2014;Nilsson et al, 2018;Tucci et al, 2019). It is still unclear whether the same mechanisms that allow transgenerational inheritance in worms exist in mammals (Horsthemke, 2018).…”

Section: Discussionmentioning

confidence: 99%

“…Different human diseases, for example a number of imprinting-associated syndromes (Angelman syndrome, Prader-Willi syndrome, and Beckwith-Wiedemann syndrome) arise due to inheritance of parental information which is not encoded in the DNA sequence (Tucci et al, 2019). In addition, while the mechanisms are still unclear, many widespread disorders were suggested to be influenced by non-genetic inheritance and to be affected by the ancestors' life history (Bohacek and Mansuy, 2015;Chen et al, 2016;Gapp et al, 2014;Kazachenka et al, 2018;Nilsson et al, 2018;Öst et al, 2014;Skvortsova et al, 2018;Teperino et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

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Stress Resets Transgenerational Small RNA Inheritance

Houri-Zeevi

Teichman

Gingold

et al. 2019

Preprint

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Transgenerational inheritance of small RNAs is challenging basic concepts of heredity and achieving control over such responses is of great interest. In C. elegans nematodes, small RNAs are transmitted across generations to establish a transgenerational memory trace of ancestral environments and distinguish self from non-self genes. Inheritance of small RNAs is regulated by dedicated machinery and carryover of aberrant heritable small RNA responses was shown to be maladaptive and to induce sterility. Here we show that various types of stress (starvation, high temperatures, and high osmolarity) but not non-stressful changes in cultivation conditions, lead to resetting of small RNA inheritance. We found that stress leads to a genome-wide reduction in heritable small RNA levels and that mutants defective in different stress pathways exhibit irregular RNAi inheritance dynamics. Moreover, we discovered that resetting of heritable RNAi is orchestrated by MAPK pathway factors, the transcription factor SKN-1, and the MET-2 methyltransferase. Termination of small RNA inheritance, and the fact that this process depends on stress, could protect from run-on of environment-

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Stress Resets Transgenerational Small RNA Inheritance

Houri-Zeevi

Teichman

Gingold

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…".bam" files from merged biological replicates were loaded into the R package metagene (v2.14.0), and coverage (RPM) was calculated at the seed site and the flanking 500 nt. The metagene profile for imprinted genes contains all conserved, predicted seed sites active miR-379/410 in maternally-expressed or paternally-expressed protein-coding genes from (Tucci et al, 2019).…”

Section: Metagene Analysismentioning

confidence: 99%

Imprinted maternally-expressed microRNAs antagonize paternally-driven gene programs in neurons

Whipple

Jacobs

Breton-Provencher

et al. 2019

Preprint

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Imprinted genes with parental-biased expression are hypothesized to result from an evolutionary conflict between the parental genomes over procurement of maternal resources.Accordingly, imprinted genes are enriched in pathways regulating nutrient acquisition, energy homeostasis, and growth. Here, we functionally characterize a large cluster of maternallyexpressed microRNAs (miRNAs) to explore why they evolved imprinted expression in neurons.Using an induced neuron (iN) culture system, we show maternally-expressed miRNAs from the miR-379/410 cluster repress paternally-expressed genes, including known regulators of energy homeostasis Plagl1 and Peg3. Additional non-imprinted metabolic regulators are also cotargeted by miR-379/410. Maternal deletion of this imprinted miRNA cluster results in derepression of its targets and up-regulation of a broader gene program regulating feeding behavior and synaptic transmission. These data suggest non-coding RNAs actively engage in parental genomic conflict, whereby maternally-expressed miRNAs antagonize paternally-driven gene programs in neurons.

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“…By far the largest such group includes thousands of genes subject to autosomal monoallelic expression (MAE, (Chess, 2016;Khamlichi and Feil, 2018;Savova et al, 2013)). MAE is an epigenetic process distinct from genetic imprinting (Tucci et al, 2019) and largely analogous to Xchromosome inactivation (XCI) (Galupa and Heard, 2018) in determination of the allelic choice ( Fig.1A, left). Like in XCI, the choice of the active allele for autosomal MAE genes is initially random and is not defined by the parent of origin.…”

Section: Introductionmentioning

confidence: 99%

DNA methylation is a key mechanism for maintaining monoallelic expression on autosomes

Gupta

Vigneau

et al. 2020

Preprint

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Thousands of mammalian genes show epigenetically controlled unequal transcription of the parental alleles. Genes subject to autosomal monoallelic expression (MAE) display mitotically stable allelic choice, leading to persistent transcriptional differences between clonal cell lineages. Mechanism of MAE mitotic maintenance is unknown. Using a new screening-by-sequencing strategy, we uncovered a key role for DNA methylation in MAE maintenance. Subset of MAE loci were insensitive to DNA demethylation, suggesting mechanistic heterogeneity of MAE. Genome-wide analyses indicate that MAE is part of a more general mode of gene regulation and reveal a previously unappreciated interplay of genetic and epigenetic control of allele-specific transcription. While cis-acting regulation defines a common underlying state for all cells, DNA methylation plays the role of an allele-specific rheostat and determines multiple regulatory states distinguishing between developmentally equivalent clonal cell lineages. Our findings imply that allele-specific analyses of clonal cell populations can unmask longterm transcriptional responses to drug-driven perturbations.

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Genomic Imprinting and Physiological Processes in Mammals

Cited by 426 publications

References 116 publications

Stress Resets Transgenerational Small RNA Inheritance

Stress Resets Transgenerational Small RNA Inheritance

Imprinted maternally-expressed microRNAs antagonize paternally-driven gene programs in neurons

DNA methylation is a key mechanism for maintaining monoallelic expression on autosomes

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