Genetics

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

Microbiota impact Drosophila ageing via Acetobacter, Tachykinin, and TkR99D

1. Diana Marcu
2. David R Sannino
3. Anthony J Dornan
4. Rita Ibrahim
5. Atharv Kapoor
6. Miriam Wood
7. Adam J Dobson

• Curated by eLife

  eLife Assessment

  This important study demonstrates that in Drosophila melanogaster, tachykinin (Tk) expression is regulated by the microbiota. The authors present convincing evidence that axenic flies raised with no microbiota are longer-lived than conventionally reared animals, and that Tk expression and Tk receptors in the nervous system are required for this effect. They further test individual bacterial strains for their role in these effects and connect the effect to loss of lipid stores and suggest that FOXO may be involved in the phenotype, results that are of interest to the fields of environmental perception, host microbiome interactions, and geroscience.

  [Editors' note: this paper was reviewed by Review Commons.]

Reviewed by eLife, Review Commons

Differential functions of upstream and intronic HOT regions shape dlg-1 transcription and C. elegans development

1. Cristina Tocchini
2. Fanny Eggeler
3. Palmer Bassett
4. Susan E. Mango

Reviewed by Review Commons

Endogenous corazonin signaling modulates the post-mating switch in behavior and physiology in females of the brown planthopper and Drosophila

1. Ning Zhang
2. Shao-Cong Su
3. Ruo-Tong Bu
4. Yi-Jie Zhang
5. Lei Yang
6. Jie Chen
7. Dick R Nässel
8. Cong-Fen Gao
9. Shun-Fan Wu

• Curated by eLife

  eLife Assessment

  This important study presents convincing evidence that uncovers a novel signaling axis impacting the post-mating response in females of the brown planthopper. The findings open several avenues for testing the molecular and neurobiological mechanisms of mating behavior in insects, although broad concerns remain about the relevance of some claims.

Reviewed by eLife

Acute opioid responses are modulated by dynamic interactions of Oprm1 and Fgf12

1. Paige M Lemen
2. Yanning Zuo
3. Alexander S Hatoum
4. Price E Dickson
5. Guy Mittleman
6. Arpana Agrawal
7. Benjamin C Reiner
8. Wade Berrettini
9. David G Ashbrook
10. Mustafa Hakan Gunturkun
11. Xusheng Wang
12. Megan K Mulligan
13. Caleb J Browne
14. Eric J Nestler
15. Francesca Telese
16. Robert W Williams
17. Hao Chen

• Curated by eLife

  eLife Assessment

  This study integrates large-scale behavioral, genetic, and molecular analyses in animal models to investigate morphine response. Utilizing high-quality, time-series Quantitative Trait Loci (QTL) mapping, the work provides compelling evidential support for novel, time-dependent genetic interactions (epistasis). A fundamental result of this rigorous analysis is the discovery of a novel Oprm1-Fgf12-MAPK signaling pathway, which offers new insights into the mechanisms of opioid sensitivity.

Reviewed by eLife

Nucleosome Positioning Shapes Cryptic Antisense Transcription

1. Jian Yi Kok
2. Zachary H. Harvey
3. Elin Axelsson
4. Frédéric Berger

Reviewed by Review Commons

Redox Dyshomeostasis Links Renal and Neuronal Dysfunction in Drosophila Models of Gaucher and Parkinson’s Disease

1. Alexander J Hull
2. Magda L Atilano
3. Kerri J Kinghorn

• Curated by eLife

  eLife Assessment

  This is a valuable manuscript that reframes Gaucher's disease pathology through the analysis of renal health, using a Drosophila model mutant for glucocerebrosidase (GBA1). The authors provide physiological and cellular data showing that renal dysfunction may be a critical disease-modifying feature. This work broadens the field's focus beyond the nervous system to include systemic ionic regulation as a potential contributor to disease initiation and progression. The genetic and experimental approaches are solid and offer a rationale for investigating analogous dysfunction in human tissues; however, several claims extend beyond the presented evidence and would benefit from additional experimental support to fully support the conclusions.

Reviewed by eLife

Abundant Parent-of-origin Effect eQTL: The Framingham Heart Study

1. Yongtao Guan
2. Tianxiao Huan
3. Daniel Levy

• Curated by eLife

  eLife Assessment

  This important study provides a systematic investigation of parent-of-origin (POE) effects on gene expression using large trio-based data from the Framingham Heart Study, uncovering thousands of potentially novel associations. While the findings are potentially significant, the statistical support for classifying POE eQTLs and some downstream analyses is incomplete, and more stringent re-analysis is needed. With such revisions, the work would serve as a foundation for advancing understanding of POEs and their role in gene regulation.

Reviewed by eLife