B lineage priming by pioneer transcription factor EBF1 requires the function of an intrinsically disordered region (IDR). Here, we examine the role of regularly spaced tyrosines in the IDR as potential determinants of IDR function and activity of EBF1. We found that four Y > A mutations in EBF1 reduced the formation of condensates in vitro and subdiffractive clusters in vivo.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
November 2022
The establishment of de novo chromatin accessibility in lymphoid progenitors requires the "pioneering" function of transcription factor (TF) early B cell factor 1 (EBF1), which binds to naïve chromatin and induces accessibility by recruiting the BRG1 chromatin remodeler subunit. However, it remains unclear whether the function of EBF1 is continuously required for stabilizing local chromatin accessibility. To this end, we replaced EBF1 by EBF1-FKBP in pro-B cells, allowing the rapid degradation by adding the degradation TAG13 (dTAG13) dimerizer.
View Article and Find Full Text PDFTranscription factor EBF1 (early B cell factor 1) acts as a key regulator of B cell specification. The transcriptional network in which EBF1 operates has been extensively studied; however, the regulation of EBF1 function remains poorly defined. By mass spectrometric analysis of proteins associated with endogenous EBF1 in pro-B cells, we identified the nuclear import receptor Transportin-3 (Tnpo3) and found that it interacts with the immunoglobulin-like fold domain of EBF1.
View Article and Find Full Text PDFGain-of-function NOTCH1 mutations drive oncogenic MYC expression in T-ALL cells. Zhou et al. (2022) reveal that Notch-targeted therapy-resistant T-ALL cells activate EBF1, which promotes a T-to-B lineage shift and maintains oncogenic MYC expression in the absence of Notch signaling.
View Article and Find Full Text PDFand mutations are associated with the development of B progenitor acute lymphoblastic leukemia (B-ALL) in humans. To understand the molecular networks driving leukemia in the (dHet) mouse model for B-ALL, we interrogated the transcriptional profiles and chromatin status of leukemic cells, preleukemic dHet pro-B, and wild-type pro-B cells with the corresponding EBF1 and Pax5 cistromes. In dHet B-ALL cells, many EBF1 and Pax5 target genes encoding pre-BCR signaling components and transcription factors were down-regulated, whereas Myc and genes downstream from IL-7 signaling or associated with the folate pathway were up-regulated.
View Article and Find Full Text PDFN-methyladenosine RNA (mA) is a prevalent messenger RNA modification in vertebrates. Although its functions in the regulation of post-transcriptional gene expression are beginning to be unveiled, the precise roles of mA during development of complex organisms remain unclear. Here we carry out a comprehensive molecular and physiological characterization of the individual components of the methyltransferase complex, as well as of the YTH domain-containing nuclear reader protein in Drosophila melanogaster.
View Article and Find Full Text PDFAlthough many authors have reported several beneficial effects ascribed to xylan, such as inhibitory action on mutagenicity activity, antiphlogistic effects, and mitogenic and comitogenic activities, few papers have investigated a systematic study on the technological properties of this polymer. The aim of the present work was to evaluate xylan as a promise raw material for the pharmaceutical industry. The water-insoluble xylan samples were extracted from corn cobs following several steps.
View Article and Find Full Text PDFA mixture of eight steroids was separated by HPLC on a silica hydride-based stationary phase modified with a moiety of cholesteryl 10-undecanoate. Within the steroid mixture progesterone showed the longest retention time suggesting the strongest interaction with the stationary phase material. To obtain more detailed information upon the effective separation process, interaction studies were performed by high resolution/magic angle spinning (HR/MAS) NMR spectroscopy recorded in the suspended state.
View Article and Find Full Text PDFReversed-phase materials with branched and unbranched alkyl groups were prepared by modifying porous, spherical silica gel in a two-step reaction-immobilization of a trifunctional alkoxysilane (3-glycidoxypropyltrimethoxysilane) on the silica surface followed by reaction with a branched and an unbranched octanoic acid. The chromatographic sorbents were characterized by solid-state (29)Si and (13)C NMR spectroscopy. The chromatographic behaviour of the stationary phases was evaluated by use of a test mixture according to the Standard Reference Material 870 set from the US National Institute of Standards and Technology, in order to study the effect of branched and unbranched alkyl chains.
View Article and Find Full Text PDFAn overview upon modern analytical techniques for the isolation, separation, and structural identification of the essential bioactive carotenoid bixin is given. Isolation from biological matrices is performed by matrix solid phase dispersion (MSPD). The extract is separated with shape-selective C(30 )columns.
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