Publications by authors named "Lachance C"
The epigenetic cofactor ENL (eleven-nineteen-leukemia) and the acetyltransferase MOZ (monocytic leukemia zinc finger) have vital roles in transcriptional regulation and are implicated in aggressive forms of leukemia. Here, we describe the mechanistic basis for the intertwined association of ENL and MOZ. Genomic analysis shows that ENL and MOZ co-occupy active promoters and that MOZ recruits ENL to its gene targets.
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- The NuA4/TIP60 complex plays a crucial role in gene regulation and maintaining genome stability by incorporating histone variant H2A.Z and acetylating histones H4, H2A, and H2A.Z.
- Cryo-electron microscopy studies reveal that the EP400 subunit acts as a scaffold, organizing the complex and ensuring correct positioning of functional modules, including the actin-related protein module.
- Loss of the TRRAP subunit disrupts the organization of the NuA4/TIP60 complex, leading to mislocalization and altered acetylation of H2A.Z, highlighting the essential functions of this assembly in cellular processes.
Article Synopsis
- MLL4 and MLL3 are proteins often mutated in cancer that modify histones, specifically monomethylating histone H3K4, and contain unexplored PHD finger domains.
- The PHD2 and PHD3 fingers of MLL4 and MLL3 interact with ASXL2, a component of the PR-DUB complex, which plays a role in regulating histone modifications.
- Analysis shows that the MLL3/4 and PR-DUB complexes work together in a way that relies on the binding of ASXL1/2, which is essential for recruiting the deubiquitinase BAP1 to active enhancers in embryonic stem cells.
Background And Objectives: Data on urinary tract infections (UTIs) in very preterm neonates (VPTNs) are scarce. We aimed to (i) describe the characteristics of UTIs in VPTNs and (ii) compare the diagnostic practices of neonatal clinicians to established pediatric guidelines.
Methods: All VPTNs (<29 weeks GA) with a suspected UTI at the CHU Sainte-Justine neonatal intensive care unit from January 1, 2014, and December 31, 2019, were included and divided into two definition categories: Possible UTI, and Definite UTI.
Article Synopsis
- JADE is a key part of the HBO1 acetyltransferase complex, which plays a significant role in regulating gene transcription and developmental processes.
- The PZP domain of JADE binds to histone H3 and DNA, facilitating the recruitment of the HBO1 complex to chromatin and influencing its enzymatic activity based on the methylation status of H3K4.
- JADE’s involvement is linked to leukemogenesis, enhancing the activity of specific fusion proteins, indicating its critical role in both normal and pathological cellular functions.
Introduction And Hypothesis: Urinary incontinence (UI) is prevalent among older women, but conservative treatment rates remain low due to limited accessibility, despite evidence supporting pelvic floor muscle training (PFMT) efficacy. Group-based approaches, including online options, could offer cost-effective alternatives. Recent evidence supports the feasibility of online group-based PFMT for treating UI in older women.
View Article and Find Full Text PDFCongenitally acquired cytomegalovirus (CMV) infection is the most prevalent congenital infection worldwide and the most frequent cause of acquired sensorineural hearing loss. The burden of the disease is even more important in premature and very low birth weight infants. However, few data exist on the treatment with intravenous ganciclovir and oral valganciclovir in this vulnerable population.
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- Human acetyltransferases MOZ and MORF play a role in aggressive leukemias due to chromosomal translocations involving their amino terminus, but the specifics of this function were unclear.
- Researchers identified two winged helix (WH) domains in both MOZ and MORF, which bind to DNA—particularly unmethylated CpG sequences—and promote gene transcription through H3K23 acetylation.
- Advanced studies (like Cryo-EM and mass spectrometry) revealed the DNA-binding mechanisms of these domains, suggesting potential therapeutic approaches for diseases linked to abnormal MOZ/MORF activities.
Article Synopsis
- The study focuses on how the envelope (E) protein of SARS-CoV-2 interacts with the human BRD4 protein.
- It presents a detailed protocol using NMR spectroscopy to analyze this interaction and to observe the effects of BRD4 inhibitors on infected lung cells.
- The methodology can also be adapted for research on other interactions between viral and human proteins, with further details available in Vann et al. (2022).
Objective: To assess the educational and clinical impact of a tiny baby intubation team (TBIT).
Study Design: Retrospective study comparing endotracheal intubation (ETI) performed: pre-implementation of a TBIT (T1), 6 months post-implementation (T2), and 4 years post-implementation (T3).
Results: Post-implementation (T2), first-attempt success rate in tiny babies increased (44% T1; 59% T2, p = 0.
Article Synopsis
- New variants of SARS-CoV-2 and drug resistance highlight the need for novel treatments against the virus.
- The study investigates how the E protein of SARS-CoV-2 interacts with the human protein BRD4, revealing that the E protein is modified (acetylated) and binds to BRD4.
- Inhibitors targeting BRD4 reduce the virus's ability to infect lung cells, suggesting BRD4 could be a promising target for anti-COVID-19 therapies.
Chromosomal translocations frequently promote carcinogenesis by producing gain-of-function fusion proteins. Recent studies have identified highly recurrent chromosomal translocations in patients with endometrial stromal sarcomas (ESSs) and ossifying fibromyxoid tumors (OFMTs), leading to an in-frame fusion of PHF1 (PCL1) to six different subunits of the NuA4/TIP60 complex. While NuA4/TIP60 is a coactivator that acetylates chromatin and loads the H2A.
View Article and Find Full Text PDFMRG15/MORF4L1 is a highly conserved protein in eukaryotes that contains a chromodomain (CHD) recognizing methylation of lysine 36 on histone H3 (H3K36me3) in chromatin. Intriguingly, it has been reported in the literature to interact with several different factors involved in chromatin modifications, gene regulation, alternative mRNA splicing, and DNA repair by homologous recombination. To get a complete and reliable picture of associations in physiological conditions, we used genome editing and tandem affinity purification to analyze the stable native interactome of human MRG15, its paralog MRGX/MORF4L2 that lacks the CHD, and MRGBP (MRG-binding protein) in isogenic K562 cells.
View Article and Find Full Text PDFBackground: Injurious falls in hospitals and care homes are a life-limiting and costly international issue. Shock-absorbing flooring may offer part of the solution; however, evidence is required to inform decision-making.
Objectives: The objectives were to assess the clinical effectiveness and cost-effectiveness of shock-absorbing flooring for fall-related injury prevention among older adults in care settings.
Article Synopsis
- The study focuses on the role of the NuA4 acetyltransferase complex in the plant Arabidopsis, particularly analyzing its scaffold proteins AtEPL1 and AtEAF1.* -
- Loss of AtEAF1 leads to impaired growth and chloroplast development, with even more severe effects observed in AtEPL1 mutants; this is linked to the regulation of nuclear plastid genes and Golden2-Like transcription factors.* -
- The research shows that AtEPL1 is critical for the acetylation of specific histones; when it’s lost, key chloroplast-related genes are downregulated, and there's a risk of incorrectly activating stress response genes.*
Background: Shock-absorbing flooring may minimise impact forces incurred from falls to reduce fall-related injuries; however, synthesized evidence is required to inform decision-making in hospitals and care homes.
Methods: This is a Health Technology Assessment mixed methods systematic review of flooring interventions targeting older adults and staff in care settings. Our search incorporated the findings from a previous scoping review, MEDLINE, AgeLine, and Scopus (to September 2019) and other sources.
Background: Anemia of prematurity is common in extremely preterm neonates, and oxygen exposure may participate to anemia by inhibiting erythropoietin secretion. We aimed to determine whether hyperoxia exerts an independent role in the occurrence of the anemia of prematurity.
Methods: Sprague-Dawley pups were exposed to 80% oxygen or room air from days 3 to 10 of life.
Approaches to Study Native Chromatin-Modifying Complex Activities and Functions.
Front Cell Dev Biol
September 2021
Article Synopsis
- The study of histone modifications is essential for understanding how genes are expressed and stabilized in the genome.
- These modifications are often influenced by complex groups of enzymes that interact with histones and help define epigenetic markers.
- The article outlines methods to purify chromatin-modifying complexes from mammalian cells and introduces a new technique for quickly depleting essential modifiers, providing standardized protocols for researchers.