The DNA methyltransferase inhibitor 5-azacytidine specifically alters the expression of helix–loop–helix proteins Id1, Id2 and Id3 during neuronal differentiation

Ebf1/Olf-1 belongs to a small multigene family encoding closely related helix-loop-helix transcription factors, which have been proposed to play a role in neuronal differentiation. Here we show that Ebf1 controls cell differentiation in the murine embryonic striatum, where it is the only gene of the family to be expressed. Ebf1 targeted disruption affects postmitotic cells that leave the subventricular zone (SVZ) en route to the mantle: they appear to be unable to downregulate genes normally restricted to the SVZ or to activate some mantle-specific genes. These downstream genes encode a variety of regulatory proteins including transcription factors and proteins involved in retinoid signalling as well as adhesion/guidance molecules. These early defects in the SVZ/mantle transition are followed by an increase in cell death, a dramatic reduction in size of the postnatal striatum and defects in navigation and fasciculation of thalamocortical fibres travelling through the striatum. Our data therefore show that Ebf1 plays an essential role in the acquisition of mantle cell molecular identity in the developing striatum and provide information on the genetic hierarchies that govern neuronal differentiation in the ventral telencephalon.

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The homeodomain-containing gene Xdbx inhibits neuronal differentiation in the developing embryo

Development ◽

10.1242/dev.127.13.2945 ◽

2000 ◽

Vol 127 (13) ◽

pp. 2945-2954 ◽

Cited By ~ 1

Author(s):

A.A. Gershon ◽

J. Rudnick ◽

L. Kalam ◽

K. Zimmerman

Keyword(s):

Neuronal Differentiation ◽

Normal Development ◽

Early Embryo ◽

Neural Plate ◽

Neural Progenitors ◽

Expression Domain ◽

Basic Helix Loop Helix ◽

Helix Loop Helix ◽

Early Neurogenesis

The development of the vertebrate nervous system depends upon striking a balance between differentiating neurons and neural progenitors in the early embryo. Our findings suggest that the homeodomain-containing gene Xdbx regulates this balance by maintaining neural progenitor populations within specific regions of the neuroectoderm. In posterior regions of the Xenopus embryo, Xdbx is expressed in a bilaterally symmetric stripe that lies at the middle of the mediolateral axis of the neural plate. This stripe of Xdbx expression overlaps the expression domain of the proneural basic/helix-loop-helix-containing gene, Xash3, and is juxtaposed to the expression domains of Xenopus Neurogenin related 1 and N-tubulin, markers of early neurogenesis in the embryo. Xdbx overexpression inhibits neuronal differentiation in the embryo and when co-injected with Xash3, Xdbx inhibits the ability of Xash3 to induce ectopic neurogenesis. One role of Xdbx during normal development may therefore be to restrict spatially neuronal differentiation within the neural plate, possibly by altering the neuronal differentiation function of Xash3.

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Prostaglandin E2 Reverses the Effects of DNA Methyltransferase Inhibitor and TGFB1 on the Conversion of Naive T Cells to iTregs

Transfusion Medicine and Hemotherapy ◽

10.1159/000502582 ◽

2019 ◽

Vol 47 (3) ◽

pp. 244-253

Author(s):

Mehmet Sahin ◽

Emel Sahin

Keyword(s):

T Cells ◽

Prostaglandin E2 ◽

Dna Methyltransferase ◽

Transforming Growth Factor ◽

Transforming Growth Factor Β ◽

Naive T Cells ◽

Naïve T Cells ◽

Dna Methyltransferase Inhibitor

Naturally occurring regulatory T cells (nTregs) are produced under thymic (tTregs) or peripherally induced (pTregs) conditions in vivo. On the other hand, Tregs generated from naive T cells in vitro under some circumstances, such as treatment with transforming growth factor-β (TGFB), are called induced Tregs (iTregs). Tregs are especially characterized by FOXP3 expression, which is mainly controlled by DNA methylation. nTregs play important roles in the suppression of immune response and self-tolerance. The prostaglandin E2 (PGE2) pathway was reported to contribute to regulatory functions of tumor-infiltrating nTregs. In this study, we examined whether PGE2 contributes to the formation of iTregs treated with TGFB1 and 5-aza-2′-deoxycytidine (5-aza-dC), which is a DNA methyltransferase inhibitor. We found that the protein and gene expression levels of FOXP3 and IL-10 were increased in 5-aza-dC and TGFB1-treated T cells in vitro. However, the addition of PGE2 to these cells reversed these increments significantly. In CFSE-based cell suppression assays, we demonstrated that PGE2 decreased the suppressive functions of 5-aza-dC and TGFB1-treated T cells.

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