Gfi-1B is a transcriptional repressor essential for the regulation of erythropoiesis and megakaryopoiesis. Here we identify Gfi-1B p32, a Gfi-1B isoform, as essential for erythroid differentiation. ...Gfi-1B p32 is generated by alternative splicing and lacks the two first zinc finger domains of the protein. Selective knock down of Gfi-1B p32 compromises erythroid differentiation, whereas its ectopic expression induces erythropoiesis in the absence of erythropoietin. Gfi-1B p32 isoform binds to Gfi-1B target gene promoters and associates with the LSD1-CoREST repressor complex more efficiently than the major Gfi-1B p37 isoform. Furthermore, we show that Gfi-1B includes a KSKK motif in its SNAG domain, which recruits the repressor complex only when dimethylated on lysine 8. Mutation of lysine 8 prevents Gfi-1B p32-induced erythroid development. Our results thus highlight a key role for the alternatively spliced Gfi-1B p32 isoform in erythroid development.
Mineral dust aerosols, produced by wind erosion in arid regions and semi-arid surfaces, are important components of the atmosphere that affect the Earth radiative budget, atmospheric chemistry and ...biogeochemical cycles. Dust aerosol particles are composed of a complex mixture of various minerals, mainly clays, calcite, quartz, feldspars and iron oxides. The nature and the relative abundance of the minerals are key parameters to evaluate mineral dust environmental impacts. Strong limitations remain to quantify the mineralogical composition of dust particles, mainly due to the low mass of in-situ collected dust particle samples. In this study, an analytical method and X-Ray Diffraction (XRD) measurements are presented to quantify the mineralogical composition of low mass aerosol particle samples. The method is applied on reference minerals (illite, kaolinite and palygorskite) commonly present in desert dust aerosols, as well as on lab-generated dust aerosols from desert soils. XRD measurements of theses samples in rotation in a glass capillary are combined with the Rietveld refinement method. The results obtained are repeatable and confronted to theoretical values given in the literature for the reference minerals. This method allows us to quantify the mineralogical composition of low mass dust mineral samples with an unprecedented accuracy.
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•A new procedure to quantify the mineralogical composition of dust aerosol samples is presented.•X-Ray Diffraction measurements performed on randomly oriented particles samples are combined with a Rietveld refinement.•Applied to reference minerals, our procedure has proved to provide results both repeatable and similar to theoretical values.•Crystalline phases of low mass mineral aerosol samples, including clays, are quantified with an unprecedented accuracy.
Aberrant activation of AKT disturbs the proliferation, survival and metabolic homeostasis of various human cancers. Thus, it is critical to understand the upstream signalling pathways governing AKT ...activation. Here, we report that AKT undergoes SETDB1-mediated lysine methylation to promote its activation, which is antagonized by the Jumonji-family demethylase KDM4B. Notably, compared with wild-type mice, mice harbouring non-methylated mutant Akt1 not only exhibited reduced body size but were also less prone to carcinogen-induced skin tumours, in part due to reduced AKT activation. Mechanistically, the interaction of phosphatidylinositol (3,4,5)-trisphosphate with AKT facilitates its interaction with SETDB1 for subsequent AKT methylation, which in turn sustains AKT phosphorylation. Pathologically, genetic alterations, including SETDB1 amplification, aberrantly promote AKT methylation to facilitate its activation and oncogenic functions. Thus, AKT methylation is an important step, synergizing with PI3K signalling to control AKT activation. This suggests that targeting SETDB1 signalling could be a potential therapeutic strategy for combatting hyperactive AKT-driven cancers.
Many prospective studies have shown that a diet enriched in omega-3 polyunsaturated fatty acids (n-3 PUFAs) can improve cognitive function during normal aging and prevent the development of ...neurocognitive diseases. However, researchers have not elucidated how n-3 PUFAs are transferred from the blood to the brain or how they relate to cognitive scores. Transport into and out of the central nervous system depends on two main sets of barriers: the blood-brain barrier (BBB) between peripheral blood and brain tissue and the blood-cerebrospinal fluid (CSF) barrier (BCSFB) between the blood and the CSF. In this review, the current knowledge of how lipids cross these barriers to reach the CNS is presented and discussed. Implications of these processes in health and disease, particularly during aging and neurodegenerative diseases, are also addressed. An assessment provided here is that the current knowledge of how lipids cross these barriers in humans is limited, which hence potentially restrains our capacity to intervene in and prevent neurodegenerative diseases.
Like protein-coding genes, long noncoding RNA (lncRNA) genes are composed of introns and exons. After their transcription, lncRNAs are subject to constitutive and/or alternative splicing. Here, we ...describe the current knowledge on lncRNA splice variants and their functional implications in cell biology.
Aims
Cheap, rapid tools for measuring emissions of Plasmopara viticola sporangia directly in the field are required to protect grapevines efficiently and sustainably against downy mildew. To this ...end, we adapted an existing loop‐mediated isothermal amplification (LAMP) protocol based on ITS2 sequences, coupled with a rotating‐arm sampler and simple cell lysis, for the in‐field measurement of airborne sporangia of P. viticola.
Methods and Results
We estimated the sensitivity and specificity of the molecular reaction with an unpurified DNA template in controlled conditions, using the droplet digital PCR (ddPCR) as a reference. We show that the LAMP lower limit of quantification is 3.3 sporangia.m−3 air sampled. Cell lysis in KOH solution was less efficient than CTAB for DNA extraction, but the repeatability of the method was good. We tested this protocol directly in a plot at Chateau Dillon (Blanquefort, France) in which we monitored P. viticola sporangia concentrations from March to October 2020 (88 samples which revealed concentrations ranging from 0 to 243 sporangia.m−3). There was a significant quantitative correlation (R2 = 0.52) between ddPCR and LAMP results.
Conclusion
LAMP analysis of an unpurified DNA matrix is a simple and reliable method for in‐field estimations of the concentration of airborne P. viticola sporangia.
Significance and Impact of the Study
This study constitutes a first step towards the development of a regional grapevine downy mildew monitoring network in the vineyards of Bordeaux.
Lysine-specific demethylase 1 (LSD1) has been reported to repress and activate transcription by mediating histone H3K4me1/2 and H3K9me1/2 demethylation, respectively. The molecular mechanism that ...underlies this dual substrate specificity has remained unknown. Here we report that an isoform of LSD1, LSD1+8a, does not have the intrinsic capability to demethylate H3K4me2. Instead, LSD1+8a mediates H3K9me2 demethylation in collaboration with supervillin (SVIL), a new LSD1+8a interacting protein. LSD1+8a knockdown increases H3K9me2, but not H3K4me2, levels at its target promoters and compromises neuronal differentiation. Importantly, SVIL co-localizes to LSD1+8a-bound promoters, and its knockdown mimics the impact of LSD1+8a loss, supporting SVIL as a cofactor for LSD1+8a in neuronal cells. These findings provide insight into mechanisms by which LSD1 mediates H3K9me demethylation and highlight alternative splicing as a means by which LSD1 acquires selective substrate specificities (H3K9 versus H3K4) to differentially control specific gene expression programs in neurons.
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•LSD1+8a isoform does not have the intrinsic property to demethylate H3K4•LSD1+8a functions as a co-activator by demethylating the repressive H3K9me2 mark•LSD1+8a interacts with SVIL; LSD1+8a/SVIL-containing complex demethylates H3K9me2•SVIL regulates neuronal maturation by controlling LSD1+8a mediated H3K9 demethylation
Benoit Laurent et al. find that the neuro-enriched LSD1 isoform, LSD1+8a, mediates H3K9me2 demethylation in collaboration with the supervillin protein (SVIL), a new LSD1+8a partner. These findings highlight alternative splicing as a means by which LSD1 acquires selective substrate specificities (H3K9 versus H3K4) to control specific transcriptional programs in neurons.
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