Genetics

Ecdysone acts through cortex glia to regulate sleep in Drosophila

1. Yongjun Li
2. Paula Haynes
3. Shirley L Zhang
4. Zhifeng Yue
5. Amita Sehgal

• Curated by eLife

  eLife assessment

  Li and colleague report observations that constitute a potentially fundamental advance, pointing to a mechanism by which non-neural cells can influence sleep regulation by neurons, The authors provide evidence in Drosophila showing that ecdysone synthesised outside the brain regulates sleep via ecdysone receptors in cortex glia. It further suggests that steroid signalling in glia can act on sleep through lipid droplet mobilization.

Reviewed by eLife

DNMT3B PWWP mutations cause hypermethylation of heterochromatin

1. Francesca Taglini
2. Ioannis Kafetzopoulos
3. Willow Rolls
4. Kamila Irena Musialik
5. Heng Yang Lee
6. Yujie Zhang
7. Mattia Marenda
8. Lyndsay Kerr
9. Hannah Finan
10. Cristina Rubio-Ramon
11. Philippe Gautier
12. Hannah Wapenaar
13. Dhananjay Kumar
14. Hazel Davidson-Smith
15. Jimi Wills
16. Laura C Murphy
17. Ann Wheeler
18. Marcus D Wilson
19. Duncan Sproul

Reviewed by Review Commons, PREreview

The nutrient-sensing GCN2 signaling pathway is essential for circadian clock function by regulating histone acetylation under amino acid starvation

1. Xiao-Lan Liu
2. Yulin Yang
3. Yue Hu
4. Jingjing Wu
5. Chuqiao Han
6. Qiaojia Lu
7. Xihui Gan
8. Shaohua Qi
9. Jinhu Guo
10. Qun He
11. Yi Liu
12. Xiao Liu

• Curated by eLife

  eLife assessment

  This important study provides evidence for CPC-3 mediating induction of the transcription factor CPC-1 in starved Neurospora cells, with CPC-1-mediated recruitment of Gcn5 and acetylation of the FRQ promoter counteracting the function of histone deacetylase HDA1, which in turn maintains high occupancy of the transcription factor WCC and attendant circadian rhythm of FRQ expression. The findings are significant in showing how the well-established pathways for circadian rhythm centered on FRQ gene expression and cross-pathway control centered on CPC-1 induction are integrated to maintain rhythmic cell growth in the face of amino acid limitation. However, the evidence for these claims is incomplete in certain respects and additional statistical analyses and experimental evidence are needed to better support the claims of rhythmic CPC-1 binding at FRQ, of the role of GCN-5 in rhythmic FRQ transcription in starvation conditions, and of rhythmic transcription of CPC-1-regulated amino acid biosynthetic genes.

Reviewed by eLife

Timing of TORC1 inhibition dictates Pol III involvement in longevity in Caenorhabditis elegans

1. Yasir Malik
2. Isabel Goncalves Silva
3. Rene Rivera Diazgranados
4. Colin Selman
5. Nazif Alic
6. Jennifer M. A. Tullet

Reviewed by Review Commons

Identification of a weight loss-associated causal eQTL in MTIF3 and the effects of MTIF3 deficiency on human adipocyte function

1. Mi Huang
2. Daniel Coral
3. Hamidreza Ardalani
4. Peter Spegel
5. Alham Saadat
6. Melina Claussnitzer
7. Hindrik Mulder
8. Paul W Franks
9. Sebastian Kalamajski

• Curated by eLife

  eLife assessment

  The study provides a fundamental framework for linking human genome variation to targetable mechanisms of disease. The authors provide compelling evidence that a strong candidate locus associates with body weight in humans acts through adipocyte MTIF3. Thus, the generalized approaches taken in this study have the potential to inform genetic association studies in general and lay a foundation for future functional genomics studies.

Reviewed by eLife

Live imaging reveals chromatin compaction transitions and dynamic transcriptional bursting during stem cell differentiation in vivo

1. Dennis May
2. Sangwon Yun
3. David G Gonzalez
4. Sangbum Park
5. Yanbo Chen
6. Elizabeth Lathrop
7. Biao Cai
8. Tianchi Xin
9. Hongyu Zhao
10. Siyuan Wang
11. Lauren E Gonzalez
12. Katie Cockburn
13. Valentina Greco

• Curated by eLife

  eLife assessment

  This is an important and valuable paper that uses H2B overexpression to quantify changes to chromatin compaction using elegant in vivo imaging approaches in the live epidermis in stem cells undergoing epidermal differentiation. The results confirm in vitro findings that changes to chromatin compaction precede cell fate commitment during epidermal stem cell differentiation. These conclusions are mostly supported by solid and convincing experimental and quantitative evidence and the recapitulation of chromatin and transcriptional phenomena in a live tissue setting using careful in vivo imaging and quantification is of value.

Reviewed by eLife

Bidirectional promoter activity from expression cassettes can drive off-target repression of neighboring gene translation

1. Emily Nicole Powers
2. Charlene Chan
3. Ella Doron-Mandel
4. Lidia Llacsahuanga Allcca
5. Jenny Kim Kim
6. Marko Jovanovic
7. Gloria Ann Brar

• Curated by eLife

  eLife assessment

  Powers and colleagues reveal that commonly used "genetic markers" (selectable cassettes that allow for genome modification) may lead to unintended consequences and unanticipated phenotypes. These consequences arise from cryptic expression directed from within the cassettes into adjacent genomic regions. In this work, they identify a particularly strong example of marker interference with a neighboring gene's expression and develop and test next-generation tools that circumvent the problem. The work will be primarily of interest to yeast biologists using these types of tools and interpreting these types of data.

Reviewed by eLife

Heritability enrichment in context-specific regulatory networks improves phenotype-relevant tissue identification

1. Zhanying Feng
2. Zhana Duren
3. Jingxue Xin
4. Qiuyue Yuan
5. Yaoxi He
6. Bing Su
7. Wing Hung Wong
8. Yong Wang

• Curated by eLife

  eLife assessment

  This manuscript is of interest to scientists studying the genetics of complex human diseases. The approach introduced here is potentially useful for the identification of tissues linked to complex disease heritability. Currently, the key claims of the paper are not entirely supported by the data. The claims may become well supported once the authors improve statistical rigor and perform a more comprehensive comparison with other methods.

Reviewed by eLife

Magnesium and the magnesium transporter UEX regulate sleep via Ca ²⁺ -dependent CREB signaling and a CNK-ERK pathway

1. Xin Yuan
2. Huimei Zheng
3. Xiao Xu
4. Huan Deng
5. Xiaohang Yang
6. Yongmei Xi

• Curated by eLife

  eLife assessment

  This manuscript provides valuable evidence for the role of magnesium homeostasis and relevant signaling pathway in Drosophila sleep regulation. It will be of interest to cellular biologists and neuroscientists interested in sleep:wake behavior and the potential role of magnesium in promoting sleep. Nevertheless, the evidence for the key claims of the manuscript is incomplete and is not fully supported by the data as reasonable alternative explanations exist.

Reviewed by eLife

Interdependent progression of bidirectional sister replisomes in E. coli

1. Po Jui Chen
2. Anna B McMullin
3. Bryan J Visser
4. Qian Mei
5. Susan M Rosenberg
6. David Bates

• Curated by eLife

  eLife assessment

  This paper reports a fundamental set of new results describing replisome organization and dynamics in E. coli. Cellular sites of active DNA replication (forks) spatially co-localize into structures termed replication factories, but the biological rationale for this fork co-localization has remained unknown. In an elegant study, the authors provide strong evidence that these factories are necessary to both coordinate and promote the progression of colocalized forks, and to help prevent them from spontaneously and prematurely dissociating. Through these findings, it is shown, for the first time, that replisomes' association has a beneficial impact on the bacterium. This is important work that provides robust data in favor of the factory and splitting model.

Reviewed by eLife