Genetics

Distinct chromatin regulators downmodulate meiotic axis protein deposition and DNA break induction at chromosome ends

1. Adhithi R. Raghavan
2. Kieron May
3. Vijayalakshmi V. Subramanian
4. Hannah G. Blitzblau
5. Neem J. Patel
6. Jonathan Houseley
7. Andreas Hochwagen

• Curated by eLife

  eLife Assessment

  This valuable paper describes the regulation of the association of meiotic chromosome axis proteins on chromosome ends with sub-telomeric elements in budding yeast. The genome-wide analyses of binding of chromosome components as well as chromatin regulators, complemented with the mapping of meiotic DNA double-strand breaks on chromosome ends, provided incomplete evidence to support the authors' conclusion. The results in the paper are of interest to researchers in meiotic recombination and the structure of genomes and chromosomes.

Reviewed by eLife

Functional Profiling of 2,193 ASS1 Missense Variants: Insights into Variant Pathogenicity and Epistatic Interactions in Citrullinemia Type I

1. Russell S. Lo
2. Gareth A. Cromie
3. Michelle Tang
4. Amy Sirr
5. Ljubica Caldovic
6. Hiroki Morizono
7. Nicholas Ah Mew
8. Andrea Gropman
9. Aimée M. Dudley

Reviewed by Review Commons

Maternal SETDB1 enables development beyond cleavage stages by extinguishing the MERVL-driven 2-cell totipotency transcriptional program in the mouse embryo

1. Tie-Bo Zeng
2. Zhen Fu
3. Mary F Majewski
4. Ji Liao
5. Marie Adams
6. Piroska E Szabó

• Curated by eLife

  eLife Assessment

  This study presents a valuable finding on maternal SETDB1 as a key chromatin repressor that shuts down the 2C gene program and enables normal mouse embryonic development. The evidence supporting the claims of the authors is solid, although the inclusion of a causality test, a mechanistic understanding of SETDB1 targeting, and phenotypic quantification would have greatly strengthened the study. The work will be of broad interest to biologists working on embryonic development, stem cells and gene regulation.

Reviewed by eLife

Reproducibility of Scientific Claims in Drosophila Immunity: A Retrospective Analysis of 400 Publications

1. Hannah Westlake
2. Fabrice David
3. Yao Tian
4. Kenan Krakovic
5. Asya Dolgikh
6. Liza Juravlev
7. Thomas Esmangart de Bournonville
8. Alexia Carboni
9. Claudia Melcarne
10. Tisheng Shan
11. Yang Wang
12. Yizhu Mu
13. Akshata Kotwal
14. Nadia Pirko
15. Jean Philippe Boquete
16. Fanny Schüpfer
17. Samuel Rommelaere
18. Mickael Poidevin
19. Zhonggeng Liu
20. Shu Kondo
21. Girish S Ratnaparkhi
22. Sveta Chakrabarti
23. Guiqing Liu
24. Florent Masson
25. Li Xiaoxue
26. Mark A Hanson
27. Haobo Jiang
28. Francesca Di Cara
29. Estee Kurant
30. Bruno Lemaitre

• Curated by eLife

  eLife Assessment

  This fundamental study is part of an impressive, large-scale effort to assess the reproducibility of published findings in the field of Drosophila immunity. In a companion article, the authors analyze 400 papers published between 1959 and 2011, and assess how many of the claims in these papers have been tested in subsequent publications. In this article, the authors report the results of validation experiments to assess a subset of the claims that, according to the literature, have not been corroborated. While the evidence reported for some of these validation studies is convincing, it remains incomplete for others.

Reviewed by eLife

Genetic and environmental determinants of multicellular-like phenotypes in fission yeast

1. Bence Kӧvér
2. Céleste E. Cohen
3. Markus Ralser
4. Benjamin M. Heineike
5. Jürg Bähler

Reviewed by Review Commons

Khdc3 Regulates Metabolism Across Generations in a DNA-Independent Manner

1. Liana Senaldi
2. Nora Hassan
3. Sean Cullen
4. Uthra Balaji
5. Natalie Trigg
6. Jinghua Gu
7. Hailey Finkelstein
8. Kathryn Phillips
9. Colin Conine
10. Matthew Smith-Raska

• Curated by eLife

  eLife Assessment

  This important mouse study shows that wild-type female progeny of Khdc3 mutants have abnormal gene expression relating to hepatic metabolism, which persists over multiple generations and passes through both female and male lineages. A role for small RNAs on this phenomenon is proposed, and evidence supporting the authors' claims is convincing. Further experiments are required to functionally validate the role of small RNAs in transmission of the phenotype. The work will be of interest to researchers in the field of DNA-independent mechanism of inheritance.

Reviewed by eLife

The Impact of Stability Considerations on Genetic Fine-mapping

1. Alan J Aw
2. Lionel Chentian Jin
3. Nilah M Ioannidis
4. Yun S Song

• Curated by eLife

  eLife Assessment

  This important study presents a methodologically rigorous framework for stability-guided fine-mapping, extending PICS and generalizing to methods such as SuSiE, supported by comprehensive simulations and functional enrichment analyses. The evidence is now convincing, demonstrating improved causal variant recovery and offering a robust alternative for cross-population fine-mapping. The approach will be of particular interest to statistical geneticists, computational biologists, and biomedical researchers who rely on fine-mapping to interpret genetic association signals.

Reviewed by eLife

A default silencing mechanism restrains stress-induced genes in C. elegans

1. Orkan Ilbay
2. Alejandro Rodriguez Gama
3. Daniel F Jarosz
4. Richard I Morimoto
5. Andrew Fire

• Curated by eLife

  eLife Assessment

  This valuable study identifies a novel regulator of stress-induced gene quiescence in C. elegans: the multi-Zinc-finger protein ZNF-236. The work provides evidence for an active mechanism that maintains the repressed state of inducible genes under basal conditions in the absence of stress. The claims for discovery made in the title and abstract are supported by solid experimental data. However, a deeper investigation into the mechanisms of ZNF-236 action could substantially enhance the manuscript's impact and value.

Reviewed by eLife

Fragile nucleosomes are essential for RNA Polymerase II to transcribe in eukaryotes

1. Lingbo Li
2. Samuel Hunter
3. Sonia Leach
4. Yonghua Zhuang
5. Haolin Liu
6. Junfeng Gao
7. Qianqian Zhang
8. Timothy J Stasevich
9. Hiroshi Kimura
10. Robin Dowell
11. Gongyi Zhang

• Curated by eLife

  eLife Assessment

  This study addresses an important problem in gene regulation, namely, which features of chromatin regulate potential RNA Polymerase 2 activity at a locus. The authors provided evidence that specific post-translational modifications of histones within the gene body are correlated with Pol II transcription, that these modifications are dynamic, and that they can be regulated by Pol II activity. The manuscript contributes to the concept of "fragile nucleosomes" as a unifying framework for key epigenetic drivers of transcription; however, the quality of the evidence provided is inadequate in support of the claims made, and further evidence teasing out the mechanistic aspects of the work would strengthen its impact. This work will be of interest to the fields of transcriptional regulation, chromatin structure, and epigenetics.

Reviewed by eLife

Translational reading frame determines the pathogenicity of C-terminal frameshift deletions in MeCP2: an alternative therapeutic approach

1. Jacky Guy
2. Elena Hein
3. Bea Alexander-Howden
4. Timur von Bock und Polach
5. Tricia Mathieson
6. Benjamin P Kleinstiver
7. Huda Zoghbi
8. Adrian Bird

• Curated by eLife

  eLife Assessment

  This study offers important insight into the pathogenic basis of intragenic frameshift deletions in the carboxy-terminal domain of MECP2, which account for some Rett syndrome cases, yet similar variants also appear in unaffected individuals. Using base editing and mouse models, the authors present convincing evidence supporting the pathogenicity of select deletion variants, with potential implications for therapeutic development. However, comments regarding the analysis of publicly available genetic databases should be addressed to strengthen the conclusions and provide greater clarity to the field.

Reviewed by eLife