Clock-dependent chromatin accessibility rhythms regulate circadian transcription DOI Creative Commons
Ye Yuan, Qianqian Chen, Margarita Brovkina

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Aug. 16, 2023

Abstract Chromatin organization plays a crucial role in gene regulation by controlling the accessibility of DNA to transcription machinery. While significant progress has been made understanding regulatory clock proteins circadian rhythms, how chromatin affects rhythms remains poorly understood. Here, we employed ATAC-seq (Assay for Transposase-Accessible with Sequencing) on FAC-sorted Drosophila neurons assess genome-wide over cycle. We observed oscillations at promoter and enhancer regions hundreds genes, enhanced either dusk or dawn, which correlated their peak transcriptional activity. Notably, genes were enriched E-box motifs, while those more accessible dawn VRI/PDP1-box indicating that they are regulated core feedback loops, PER/CLK VRI/PDP1, respectively. Further, complete loss per 01 null mutants, consistently throughout cycle, underscoring critical Period protein driving compaction during repression phase. Together, this study demonstrates regulation, revealing interplay between structure orchestrates precise timing biological processes day. This work further implies variations might play central generation diverse expression patterns neurons. Significance Statement development disease. In study, discovered robust elements clock-regulated neurons, found enrichment motifs exhibited dusk, higher dawn. Moreover, mutants highlights essential significance ∼24-hour rhythms.

Language: Английский

Phylogenomics of the Ecdysteroid Kinase-like (EcKL) Gene Family in Insects Highlights Roles in Both Steroid Hormone Metabolism and Detoxification DOI Creative Commons
Jack L. Scanlan, Charles Robin

Genome Biology and Evolution, Journal Year: 2024, Volume and Issue: 16(2)

Published: Jan. 31, 2024

The evolutionary dynamics of large gene families can offer important insights into the functions their individual members. While ecdysteroid kinase-like (EcKL) family has previously been linked to metabolism both steroid molting hormones and xenobiotic toxins, nearly all EcKL genes are unknown, there is little information on evolution across insects. Here, we perform comprehensive phylogenetic analyses a manually annotated set from 140 insect genomes, revealing comprised at least 13 subfamilies that differ in retention stability. Our results show only two known encode kinases belong different therefore must be spread throughout family. We provide comparative phylogenomic evidence EcKLs involved detoxification insects, with positive associations between size dietary chemical complexity, also find similar for cytochrome P450 glutathione S-transferase families. Unexpectedly, clade containing kinase positively associated host plant taxonomic diversity Lepidoptera, possibly suggesting multiple functional shifts hormone metabolism. hypotheses function robust framework future experimental studies They open promising new avenues exploring genomic basis adaptation including classically studied coevolution butterflies plants.

Language: Английский

Citations

6
Clock-dependent chromatin accessibility rhythms regulate circadian transcription DOI Creative Commons
Ye Yuan, Qianqian Chen, Margarita Brovkina

et al.

PLoS Genetics, Journal Year: 2024, Volume and Issue: 20(5), P. e1011278 - e1011278

Published: May 28, 2024

Chromatin organization plays a crucial role in gene regulation by controlling the accessibility of DNA to transcription machinery. While significant progress has been made understanding regulatory clock proteins circadian rhythms, how chromatin affects rhythms remains poorly understood. Here, we employed ATAC-seq (Assay for Transposase-Accessible with Sequencing) on FAC-sorted Drosophila neurons assess genome-wide at dawn and dusk over cycle. We observed oscillations promoter enhancer regions hundreds genes, enhanced either or dawn, which correlated their peak transcriptional activity. Notably, genes were enriched E-box motifs, while those more accessible VRI/PDP1-box indicating that they are regulated core feedback loops, PER/CLK VRI/PDP1, respectively. Further, complete loss per 01 null mutants, consistently both dusk, underscoring critical Period protein driving compaction during repression phase dawn. Together, this study demonstrates regulation, revealing interplay between structure orchestrates precise timing biological processes throughout day. This work further implies variations might play central generation diverse expression patterns neurons.

Language: Английский

Citations

6
Ensheathing glia promote increased lifespan and healthy brain aging DOI Creative Commons
Lihong Sheng, Emily J. Shields, Janko Gospočić

et al.

Aging Cell, Journal Year: 2023, Volume and Issue: 22(5)

Published: Feb. 24, 2023

Abstract Glia have an emergent role in brain aging and disease. In the Drosophila melanogaster brain, ensheathing glia function as phagocytic cells respond to acute neuronal damage, analogous mammalian microglia. We previously reported changes composition over life of ants fruit flies, including a decline relative proportion with time. How these influence health expectancy is unknown. Here, we show that but not astrocytes decrease number during aging. The remaining display dysregulated expression genes involved lipid metabolism apoptosis, which may lead droplet accumulation, cellular dysfunction, death. Inhibition apoptosis rescued age, improved neuromotor performance aged extended lifespan. Furthermore, expanded population prevented amyloid‐beta accumulation fly model Alzheimer's disease delayed premature death diseased animals. These findings suggest play vital regulating animal longevity.

Language: Английский

Citations

15
Drosophila glial system: an approach towards understanding molecular complexity of neurodegenerative diseases DOI

Shweta Shweta,

Khushboo Sharma,

Mallikarjun Shakarad

et al.

Molecular Biology Reports, Journal Year: 2024, Volume and Issue: 51(1)

Published: Nov. 12, 2024

Language: Английский

Citations

4
Glia: The Cellular Glue that binds Circadian Rhythms and Sleep DOI Creative Commons

Catarina Cavalhas-Almeida,

Amita Sehgal

SLEEP, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 15, 2025

Glia are increasingly appreciated as serving an important function in the control of sleep and circadian rhythms. Glial cells Drosophila mammals regulate daily rhythms locomotor activity well homeostatic rebound following deprivation. In addition, they contribute to proposed functions sleep, with different mapping varied glial subtypes. Here, we discuss recent findings rodent models establishing a role glia or regulation synaptic plasticity, brain metabolism, removal cellular debris immune challenges. These underscore relevance for benefits attributed have implications understanding neurobiological mechanisms underlying associated disorders.

Language: Английский

Citations

0
A carnitine transporter at the blood–brain barrier modulates sleep via glial lipid metabolism in Drosophila DOI Creative Commons

Ashley Avila,

Ava S. Lewandowski,

Yongjun Li

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(4)

Published: Jan. 23, 2025

To regulate brain function, peripheral compounds must traverse the blood–brain barrier (BBB), an interface between and circulatory system. determine whether specific transport mechanisms are relevant for sleep, we conducted a BBB-specific inducible RNAi knockdown (iKD) screen genes affecting sleep in Drosophila . We observed reduced with of solute carrier CG6126 , carnitine transporter, as determined by isotope flux. Our findings suggest that regulation is through role shuttle regulating fatty acid metabolism lipid droplets accumulate brains BBB iKD flies. Knocking down mitochondrial transferases non-BBB glial cells mimicked flies, while bypassing necessity dietary medium-chain acids or palmitoylcarnitine rescued sleep. propose via promotes necessary maintaining

Language: Английский

Citations

0
Regulation of lipid dysmetabolism and neuroinflammation linked with Alzheimer's disease through modulation of Dgat2 DOI Creative Commons
Archana Yadav,

Xiaosen Ouyang,

Morgan Barkley

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 19, 2025

Abstract Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-β (Aβ) plaque accumulation, cognitive decline, lipid dysregulation, and neuroinflammation. Mutations in the Amyloid Precursor Protein (APP), accumulation of A β42 contribute to AD, however, underlying mechanisms linking beta amyloid metabolism neuroinflammation remain unclear. Using Drosophila models, we demonstrate that App NLG Aβ42 lead locomotor impairments, disrupted sleep activity, memory deficits, loss synaptic integrity, Lipid have also been observed NLG-F knockin mouse model, supporting their involvement AD pathogenesis. Furthermore, role Diacylglycerol O-acyltransferase 2 (Dgat2), key enzyme regulation, modulating phenotypes, as Dgat2 levels its potential transcription factors were altered models. In knockdown reduced restored improved function, attenuated Additionally, modulation quality circadian rhythms, further implicating progression. mice, inhibition mitigated dysmetabolism decreased neuroinflammatory responses, expression risk genes. These findings underscore intricate interplay between pathology, neuroinflammation, suggest targeting may provide novel therapeutic strategy for mitigating AD-associated dysfunction. Understanding conserved impact homeostasis across species offers valuable insights into translational interventions AD.

Language: Английский

Citations

0
Insect nuclear receptors: From orphans to ligands DOI
Wen Liu, Hang Chen, Kirst King‐Jones

et al.

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
The Drosophila blood-brain barrier emerges as a model for understanding human brain diseases DOI Creative Commons
Esteban G. Contreras, Christian Klämbt

Neurobiology of Disease, Journal Year: 2023, Volume and Issue: 180, P. 106071 - 106071

Published: March 9, 2023

The accurate regulation of the microenvironment within nervous system is one key features characterizing complex organisms. To this end, neural tissue has to be physically separated from circulation, but at same time, mechanisms must in place allow controlled transport nutrients and macromolecules into out brain. These roles are executed by cells blood-brain barrier (BBB) found interface circulation tissue. BBB dysfunction observed several neurological diseases human. Although can considered as a consequence diseases, strong evidence supports notion that promote progression brain disorders. In review, we compile recent describing contribution Drosophila further understanding disease human patients. We discuss function during infection inflammation, drug clearance addictions, sleep, chronic neurodegenerative disorders epilepsy. summary, suggests fruit fly, melanogaster, successfully employed model disentangle underlying diseases.

Language: Английский

Citations

10
Breaking free from the clock’s tyranny restores memory to brain damaged flies DOI Open Access
Stephane Dissel,

Ellen Morgan,

Lijuan Cao

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 26, 2024

Abstract The relationship between sleep and memory is an active topic of investigation. In this context, we demonstrate that enhancing restores to flies with ablated Mushroom Bodies (MB), a key center; consistent across several assays. Mapping the underlying circuitry reveals circadian modulation subset Dopaminergic neurons (DANs) modulate aversive learning. Using imaging, show MB-ablation disrupts, time day these are most responsive. Knocking down receptor for clock output signal, Pigment-dispersing factor (Pdfr), in DANs MB-ablated flies. Crucially, does not result impairments absence functioning clock. Our results reveal neuromodulation’s role cognitive restoration, where aids damaged brains, but unexpectedly hinders process.

Language: Английский

Citations

3