journal
https://read.qxmd.com/read/38457441/the-regulation-of-methylation-on-the-z-chromosome-and-the-identification-of-multiple-novel-male-hyper-methylated-regions-in-the-chicken
#21
JOURNAL ARTICLE
Andrey Höglund, Rie Henriksen, Allison M Churcher, Carlos M Guerrero-Bosagna, Alvaro Martinez-Barrio, Martin Johnsson, Per Jensen, Dominic Wright
DNA methylation is a key regulator of eukaryote genomes, and is of particular relevance in the regulation of gene expression on the sex chromosomes, with a key role in dosage compensation in mammalian XY systems. In the case of birds, dosage compensation is largely absent, with it being restricted to two small Male Hyper-Methylated (MHM) regions on the Z chromosome. To investigate how variation in DNA methylation is regulated on the Z chromosome we utilised a wild x domestic advanced intercross in the chicken, with both hypothalamic methylomes and transcriptomes assayed in 124 individuals...
March 8, 2024: PLoS Genetics
https://read.qxmd.com/read/38452140/the-pp2a-like-phosphatase-ppg1-mediates-assembly-of-the-far-complex-to-balance-gluconeogenic-outputs-and-enables-adaptation-to-glucose-depletion
#22
JOURNAL ARTICLE
Shreyas Niphadkar, Lavanya Karinje, Sunil Laxman
To sustain growth in changing nutrient conditions, cells reorganize outputs of metabolic networks and appropriately reallocate resources. Signaling by reversible protein phosphorylation can control such metabolic adaptations. In contrast to kinases, the functions of phosphatases that enable metabolic adaptation as glucose depletes are poorly studied. Using a Saccharomyces cerevisiae deletion screen, we identified the PP2A-like phosphatase Ppg1 as required for appropriate carbon allocations towards gluconeogenic outputs-trehalose, glycogen, UDP-glucose, UDP-GlcNAc-after glucose depletion...
March 7, 2024: PLoS Genetics
https://read.qxmd.com/read/38452112/cis-regulatory-polymorphism-at-fiz-ecdysone-oxidase-contributes-to-polygenic-evolutionary-response-to-malnutrition-in-drosophila
#23
JOURNAL ARTICLE
Fanny Cavigliasso, Mikhail Savitsky, Alexey Koval, Berra Erkosar, Loriane Savary, Hector Gallart-Ayala, Julijana Ivanisevic, Vladimir L Katanaev, Tadeusz J Kawecki
We investigate the contribution of a candidate gene, fiz (fezzik), to complex polygenic adaptation to juvenile malnutrition in Drosophila melanogaster. Experimental populations maintained for >250 generations of experimental evolution to a nutritionally poor larval diet (Selected populations) evolved several-fold lower fiz expression compared to unselected Control populations. Here we show that this divergence in fiz expression is mediated by a cis-regulatory polymorphism. This polymorphism, originally sampled from a natural population in Switzerland, is distinct from a second cis-regulatory SNP previously identified in non-African D...
March 7, 2024: PLoS Genetics
https://read.qxmd.com/read/38442125/rna-cis-regulators-are-important-for-streptococcus-pneumoniae-in-vivo-success
#24
JOURNAL ARTICLE
Indu Warrier, Ariana Perry, Sara M Hubbell, Matthew Eichelman, Tim van Opijnen, Michelle M Meyer
Bacteria have evolved complex transcriptional regulatory networks, as well as many diverse regulatory strategies at the RNA level, to enable more efficient use of metabolic resources and a rapid response to changing conditions. However, most RNA-based regulatory mechanisms are not well conserved across different bacterial species despite controlling genes important for virulence or essential biosynthetic processes. Here, we characterize the activity of, and assess the fitness benefit conferred by, twelve cis-acting regulatory RNAs (including several riboswitches and a T-box), in the opportunistic pathogen Streptococcus pneumoniae TIGR4...
March 5, 2024: PLoS Genetics
https://read.qxmd.com/read/38442113/genome-evolution-and-divergence-in-cis-regulatory-architecture-is-associated-with-condition-responsive-development-in-horned-dung-beetles
#25
JOURNAL ARTICLE
Phillip L Davidson, Armin P Moczek
Phenotypic plasticity is thought to be an important driver of diversification and adaptation to environmental variation, yet the genomic mechanisms mediating plastic trait development and evolution remain poorly understood. The Scarabaeinae, or true dung beetles, are a species-rich clade of insects recognized for their highly diversified nutrition-responsive development including that of cephalic horns-evolutionarily novel, secondary sexual weapons that exhibit remarkable intra- and interspecific variation...
March 5, 2024: PLoS Genetics
https://read.qxmd.com/read/38442104/an-epigenetic-timer-regulates-the-transition-from-cell-division-to-cell-expansion-during-arabidopsis-petal-organogenesis
#26
JOURNAL ARTICLE
Ruirui Huang, Vivian F Irish
A number of studies have demonstrated that epigenetic factors regulate plant developmental timing in response to environmental changes. However, we still have an incomplete view of how epigenetic factors can regulate developmental events such as organogenesis, and the transition from cell division to cell expansion, in plants. The small number of cell types and the relatively simple developmental progression required to form the Arabidopsis petal makes it a good model to investigate the molecular mechanisms driving plant organogenesis...
March 5, 2024: PLoS Genetics
https://read.qxmd.com/read/38437248/chimeric-systems-composed-of-swapped-tra-subunits-between-distantly-related-f-plasmids-reveal-striking-plasticity-among-type-iv-secretion-machines
#27
JOURNAL ARTICLE
Kouhei Kishida, Yang Grace Li, Natsumi Ogawa-Kishida, Pratick Khara, Abu Amar M Al Mamun, Rachel E Bosserman, Peter J Christie
Bacterial type IV secretion systems (T4SSs) are a versatile family of macromolecular translocators, collectively able to recruit diverse DNA and protein substrates and deliver them to a wide range of cell types. Presently, there is little understanding of how T4SSs recognize substrate repertoires and form productive contacts with specific target cells. Although T4SSs are composed of a number of conserved subunits and adopt certain conserved structural features, they also display considerable compositional and structural diversity...
March 4, 2024: PLoS Genetics
https://read.qxmd.com/read/38437244/basement-membrane-diversification-relies-on-two-competitive-secretory-routes-defined-by-rab10-and-rab8-and-modulated-by-dystrophin-and-the-exocyst-complex
#28
JOURNAL ARTICLE
Cynthia Dennis, Pierre Pouchin, Graziella Richard, Vincent Mirouse
The basement membrane (BM) is an essential structural element of tissues, and its diversification participates in organ morphogenesis. However, the traffic routes associated with BM formation and the mechanistic modulations explaining its diversification are still poorly understood. Drosophila melanogaster follicular epithelium relies on a BM composed of oriented BM fibrils and a more homogenous matrix. Here, we determined the specific molecular identity and cell exit sites of BM protein secretory routes. First, we found that Rab10 and Rab8 define two parallel routes for BM protein secretion...
March 4, 2024: PLoS Genetics
https://read.qxmd.com/read/38437227/divergent-role-of-mitochondrial-amidoxime-reducing-component-1-marc1-in-human-and-mouse
#29
JOURNAL ARTICLE
Eriks Smagris, Lisa M Shihanian, Ivory J Mintah, Parnian Bigdelou, Yuliya Livson, Heather Brown, Niek Verweij, Charleen Hunt, Reid O'Brien Johnson, Tyler J Greer, Suzanne A Hartford, George Hindy, Luanluan Sun, Jonas B Nielsen, Gabor Halasz, Luca A Lotta, Andrew J Murphy, Mark W Sleeman, Viktoria Gusarova
Recent human genome-wide association studies have identified common missense variants in MARC1, p.Ala165Thr and p.Met187Lys, associated with lower hepatic fat, reduction in liver enzymes and protection from most causes of cirrhosis. Using an exome-wide association study we recapitulated earlier MARC1 p.Ala165Thr and p.Met187Lys findings in 540,000 individuals from five ancestry groups. We also discovered novel rare putative loss of function variants in MARC1 with a phenotype similar to MARC1 p.Ala165Thr/p.Met187Lys variants...
March 4, 2024: PLoS Genetics
https://read.qxmd.com/read/38437202/protein-subcellular-relocalization-and-function-of-duplicated-flagellar-calcium-binding-protein-genes-in-honey-bee-trypanosomatid-parasite
#30
JOURNAL ARTICLE
Xuye Yuan, Tatsuhiko Kadowaki
The honey bee trypanosomatid parasite, Lotmaria passim, contains two genes that encode the flagellar calcium binding protein (FCaBP) through tandem duplication in its genome. FCaBPs localize in the flagellum and entire body membrane of L. passim through specific N-terminal sorting sequences. This finding suggests that this is an example of protein subcellular relocalization resulting from gene duplication, altering the intracellular localization of FCaBP. However, this phenomenon may not have occurred in Leishmania, as one or both of the duplicated genes have become pseudogenes...
March 4, 2024: PLoS Genetics
https://read.qxmd.com/read/38427688/meiotic-prophase-length-modulates-tel1-dependent-dna-double-strand-break-interference
#31
JOURNAL ARTICLE
Luz María López Ruiz, Dominic Johnson, William H Gittens, George G B Brown, Rachal M Allison, Matthew J Neale
During meiosis, genetic recombination is initiated by the formation of many DNA double-strand breaks (DSBs) catalysed by the evolutionarily conserved topoisomerase-like enzyme, Spo11, in preferred genomic sites known as hotspots. DSB formation activates the Tel1/ATM DNA damage responsive (DDR) kinase, locally inhibiting Spo11 activity in adjacent hotspots via a process known as DSB interference. Intriguingly, in S. cerevisiae, over short genomic distances (<15 kb), Spo11 activity displays characteristics of concerted activity or clustering, wherein the frequency of DSB formation in adjacent hotspots is greater than expected by chance...
March 1, 2024: PLoS Genetics
https://read.qxmd.com/read/38422160/sequestrase-chaperones-protect-against-oxidative-stress-induced-protein-aggregation-and-psi-prion-formation
#32
JOURNAL ARTICLE
Zorana Carter, Declan Creamer, Aikaterini Kouvidi, Chris M Grant
Misfolded proteins are usually refolded to their functional conformations or degraded by quality control mechanisms. When misfolded proteins evade quality control, they can be sequestered to specific sites within cells to prevent the potential dysfunction and toxicity that arises from protein aggregation. Btn2 and Hsp42 are compartment-specific sequestrases that play key roles in the assembly of these deposition sites. Their exact intracellular functions and substrates are not well defined, particularly since heat stress sensitivity is not observed in deletion mutants...
February 29, 2024: PLoS Genetics
https://read.qxmd.com/read/38422114/glycan-strand-cleavage-by-a-lytic-transglycosylase-mltd-contributes-to-the-expansion-of-peptidoglycan-in-escherichia-coli
#33
JOURNAL ARTICLE
Moneca Kaul, Suraj Kumar Meher, Krishna Chaitanya Nallamotu, Manjula Reddy
Peptidoglycan (PG) is a protective sac-like exoskeleton present in most bacterial cell walls. It is a large, covalently crosslinked mesh-like polymer made up of many glycan strands cross-bridged to each other by short peptide chains. Because PG forms a continuous mesh around the bacterial cytoplasmic membrane, opening the mesh is critical to generate space for the incorporation of new material during its expansion. In Escherichia coli, the 'space-making activity' is known to be achieved by cleavage of crosslinks between the glycan strands by a set of redundant PG endopeptidases whose absence leads to rapid lysis and cell death...
February 29, 2024: PLoS Genetics
https://read.qxmd.com/read/38416769/anthracyclines-induce-cardiotoxicity-through-a-shared-gene-expression-response-signature
#34
JOURNAL ARTICLE
E Renee Matthews, Omar D Johnson, Kandace J Horn, José A Gutiérrez, Simon R Powell, Michelle C Ward
TOP2 inhibitors (TOP2i) are effective drugs for breast cancer treatment. However, they can cause cardiotoxicity in some women. The most widely used TOP2i include anthracyclines (AC) Doxorubicin (DOX), Daunorubicin (DNR), Epirubicin (EPI), and the anthraquinone Mitoxantrone (MTX). It is unclear whether women would experience the same adverse effects from all drugs in this class, or if specific drugs would be preferable for certain individuals based on their cardiotoxicity risk profile. To investigate this, we studied the effects of treatment of DOX, DNR, EPI, MTX, and an unrelated monoclonal antibody Trastuzumab (TRZ) on iPSC-derived cardiomyocytes (iPSC-CMs) from six healthy females...
February 28, 2024: PLoS Genetics
https://read.qxmd.com/read/38412177/comparison-of-clinical-geneticist-and-computer-visual-attention-in-assessing-genetic-conditions
#35
JOURNAL ARTICLE
Dat Duong, Anna Rose Johny, Suzanna Ledgister Hanchard, Christopher Fortney, Kendall Flaharty, Fabio Hellmann, Ping Hu, Behnam Javanmardi, Shahida Moosa, Tanviben Patel, Susan Persky, Ömer Sümer, Cedrik Tekendo-Ngongang, Hellen Lesmann, Tzung-Chien Hsieh, Rebekah L Waikel, Elisabeth André, Peter Krawitz, Benjamin D Solomon
The use of artificial intelligence (AI) for facial diagnostics is increasingly used in the genetics clinic to evaluate patients with potential genetic conditions. Current approaches focus on one type of AI called Deep Learning (DL). While DL- based facial diagnostic platforms have a high accuracy rate for many conditions, less is understood about how this technology assesses and classifies (categorizes) images, and how this compares to humans. To compare human and computer attention, we performed eye-tracking analyses of geneticist clinicians (n = 22) and non-clinicians (n = 22) who viewed images of people with 10 different genetic conditions, as well as images of unaffected individuals...
February 27, 2024: PLoS Genetics
https://read.qxmd.com/read/38408087/contribution-of-the-eye-and-of-opn4xa-function-to-circadian-photoentrainment-in-the-diurnal-zebrafish
#36
JOURNAL ARTICLE
Clair Chaigne, Dora Sapède, Xavier Cousin, Laurent Sanchou, Patrick Blader, Elise Cau
The eye is instrumental for controlling circadian rhythms in mice and human. Here, we address the conservation of this function in the zebrafish, a diurnal vertebrate. Using lakritz (lak) mutant larvae, which lack retinal ganglion cells (RGCs), we show that while a functional eye contributes to masking, it is largely dispensable for the establishment of circadian rhythms of locomotor activity. Furthermore, the eye is dispensable for the induction of a phase delay following a pulse of white light at CT 16 but contributes to the induction of a phase advance upon a pulse of white light at CT21...
February 26, 2024: PLoS Genetics
https://read.qxmd.com/read/38408084/maintenance-of-proteostasis-by-drosophila-rer1-is-essential-for-competitive-cell-survival-and-myc-driven-overgrowth
#37
JOURNAL ARTICLE
Pranab Kumar Paul, Shruti Umarvaish, Shivani Bajaj, Rishana Farin S, Hrudya Mohan, Wim Annaert, Varun Chaudhary
Defects in protein homeostasis can induce proteotoxic stress, affecting cellular fitness and, consequently, overall tissue health. In various growing tissues, cell competition based mechanisms facilitate detection and elimination of these compromised, often referred to as 'loser', cells by the healthier neighbors. The precise connection between proteotoxic stress and competitive cell survival remains largely elusive. Here, we reveal the function of an endoplasmic reticulum (ER) and Golgi localized protein Rer1 in the regulation of protein homeostasis in the developing Drosophila wing epithelium...
February 26, 2024: PLoS Genetics
https://read.qxmd.com/read/38408082/single-cell-rna-profiling-reveals-classification-and-characteristics-of-mononuclear-phagocytes-in-colorectal-cancer
#38
JOURNAL ARTICLE
Tiantian Ji, Haoyu Fu, Liping Wang, Jinyun Chen, Shaobo Tian, Guobin Wang, Lin Wang, Zheng Wang
Colorectal cancer (CRC) is a major cause of cancer mortality and a serious health problem worldwide. Mononuclear phagocytes are the main immune cells in the tumor microenvironment of CRC with remarkable plasticity, and current studies show that macrophages are closely related to tumor progression, invasion and dissemination. To understand the immunological function of mononuclear phagocytes comprehensively and deeply, we use single-cell RNA sequencing and classify mononuclear phagocytes in CRC into 6 different subsets, and characterize the heterogeneity of each subset...
February 26, 2024: PLoS Genetics
https://read.qxmd.com/read/38377146/trps1-modulates-chromatin-accessibility-to-regulate-estrogen-receptor-alpha-er-binding-and-er-target-gene-expression-in-luminal-breast-cancer-cells
#39
JOURNAL ARTICLE
Thomas G Scott, Kizhakke Mattada Sathyan, Daniel Gioeli, Michael J Guertin
Common genetic variants in the repressive GATA-family transcription factor (TF) TRPS1 locus are associated with breast cancer risk, and luminal breast cancer cell lines are particularly sensitive to TRPS1 knockout. We introduced an inducible degron tag into the native TRPS1 locus within a luminal breast cancer cell line to identify the direct targets of TRPS1 and determine how TRPS1 mechanistically regulates gene expression. We acutely deplete over 80 percent of TRPS1 from chromatin within 30 minutes of inducing degradation...
February 20, 2024: PLoS Genetics
https://read.qxmd.com/read/38377115/the-dna-helicase-fancj-brip1-functions-in-double-strand-break-repair-processing-but-not-crossover-formation-during-prophase-i-of-meiosis-in-male-mice
#40
JOURNAL ARTICLE
Tegan S Horan, Carolline F R Ascenção, Christopher A Mellor, Meng Wang, Marcus B Smolka, Paula E Cohen
Meiotic recombination between homologous chromosomes is initiated by the formation of hundreds of programmed double-strand breaks (DSBs). Approximately 10% of these DSBs result in crossovers (COs), sites of physical DNA exchange between homologs that are critical to correct chromosome segregation. Virtually all COs are formed by coordinated efforts of the MSH4/MSH5 and MLH1/MLH3 heterodimers, the latter representing the defining marks of CO sites. The regulation of CO number and position is poorly understood, but undoubtedly requires the coordinated action of multiple repair pathways...
February 20, 2024: PLoS Genetics
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