Genetics

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

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

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

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