SUMMARY
DNA methylation in mammals is highly dynamic during germ cell and pre-implantation development but is relatively static during development of somatic tissues. 5-hydroxymethylcytosine (5hmC), created by oxidation of 5-methylcytosine (5mC) by Tet proteins and most abundant in brain, is thought to be an intermediate towards 5mC demethylation. We investigated patterns of 5mC and 5hmC during neurogenesis in the embryonic mouse brain. 5hmC levels increase during neuronal differentiation. In neuronal cells, 5hmC is not enriched at enhancers but associates preferentially with gene bodies of activated neuronal function-related genes. Within these genes, gain of 5hmC is often accompanied by loss of H3K27me3. Enrichment of 5hmC is not associated with substantial DNA demethylation suggesting that 5hmC is a stable epigenetic mark. Functional perturbation of the H3K27 methyltransferase Ezh2 or of Tet2 and Tet3 leads to defects in neuronal differentiation suggesting that formation of 5hmC and loss of H3K27me3 cooperate to promote brain development.
miR-137 is a brain-enriched microRNA. Its role in neural development remains unknown. Here we show that miR-137 plays an essential role in controlling embryonic neural stem cell fate determination. miR-137 negatively regulates cell proliferation and accelerates neural differentiation of embryonic neural stem cells. In addition, we show that histone demethylase LSD1, a transcriptional co-repressor of nuclear receptor TLX, is a downstream target of miR-137. In utero electroporation of miR-137 in embryonic mouse brains led to premature differentiation and outward migration of the transfected cells. Introducing a LSD1 expression vector lacking the miR-137 recognition site rescued miR-137-induced precocious differentiation. Furthermore, we demonstrate that TLX, an essential regulator of neural stem cell self-renewal, represses the expression of miR-137 by recruiting LSD1 to the genomic regions of miR-137. Thus, miR-137 forms a feedback regulatory loop with TLX and LSD1 to control the dynamics between neural stem cell proliferation and differentiation during neural development.
The common neurotrophin receptor, p75 NTR , has been shown to signal in the absence of Trk tyrosine kinase receptors, including induction of neural apoptosis and activation of NF-B. However, the mechanisms by which p75 NTR initiates these intracellular signal transduction pathways are unknown. Here we report interactions between p75NTR and the six members of TRAF (tumor necrosis factor receptor-associated factors) family proteins.
Abbreviations used in this paper: BrdU, bromodeoxyuridine; CDS, coding sequence; CP, cortical plate; DCX, doublecortin; E, embryonic day; IZ, intermediate zone; p-H3 + , phospho -Histone H3 + ; RGS, Regulator of G protein Signaling; shRNA, short hairpin RNA; SVZ, subventricular zone; VZ, ventricular zone.The online version of this paper contains supplemental material.
Background
OqxAB efflux pump has been found to mediate multidrug resistance (MDR) in various bacteria over the past decades. The updates on the nature and epidemiology of OqxAB efflux pump need to be fully reviewed to broaden our understanding of this MDR determinant.
Methods
A literature search using the keyword of “oqxAB” was conducted in the online databases of Pubmed and ISI Web of Science with no restriction on the date of publication. The 87 publications were included into this review as references due to their close relevance to the nature and/or epidemiology of OqxAB efflux pump.
Results
The
oqxAB
gene generally locates on chromosome and/or plasmids flanked by IS26-like elements in clinical isolates of
Enterobacteriaceae
and
Klebsiella pneumoniae
, conferring low to intermediated resistance to quinoxalines, quinolones tigecycline, nitrofurantoin, several detergents and disinfectants (benzalkonium chloride, triclosan and SDS). It could co-spread with other antimicrobial resistance genes (
bla
CTX-M
,
rmtB
and
aac(6′)-Ib
etc.), virulence genes and heavy metal resistance genes (
pco
and
sil
operons). Both RarA (activator) and OqxR (repressor) play important roles on regulation of the expression of OqxAB.
Conclusions
The dissemination of
oqxAB
gene may pose a great risk on food safety and public health. Further investigation and understanding of the natural functions, horizontal transfer, and regulation mechanism of the OqxAB efflux pump will aid in future strategies of antimicrobial usage.
Global analysis of stem/progenitor cells promises new insight into mechanisms that govern self-renewal and cellular potential, an unresolved question of stem/progenitor cell biology. Despite rapid advance of genome-wide profiling methods, the difficulty in cell purification remains a major challenge for global analysis of somatic stem/progenitor cells. Genetic tagging with a reporter provides a powerful tool for identification and isolation of a specific mature cell type, however, for stem/progenitor cells, reporter retention by progeny may be a concern for impurity. Here we describe a genetic system combining a progenitor cell specific label with a second tag for marking differentiation. We present evidence that differential labeling of neural progenitor cells and their progeny enables prospective purification of these two cell types, whereas isolation based on a single marker compromises the purity of the intended progenitor population. Comparative expression profiling between the purified progenitors and progeny documents a neural progenitor cell transcriptome and uncovers an important role of TAM receptor tyrosine kinases in the maintenance of neural progenitor cells. This study establishes a general strategy for isolation of somatic stem/progenitor cells and provides a transcriptome database of neural progenitor cells useful for identification of causal factors of neural progenitor cell state, global dissection of epigenetic control of cellular potential, as well as for developing biomarkers or targets of brain cancer stem/initiating cells for therapeutic interventions.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.