Acetylation of Tat defines a CyclinT1-independent step in HIV transactivation

International audienceThe HIV transcriptional activator Tat is acetylated by p300 at a single lysine residue in the TAR RNA binding domain. We have generated monoclonal and polyclonal antibodies specific for the acetylated form of Tat (AcTat). Microinjection of anti-AcTat antibodies inhibited Tat-mediated transactivation in cells. Similarly, the p300 inhibitor Lys-CoA and siRNA specific for p300 suppressed Tat transcriptional activity. Full-length synthetic AcTat bound to TAR RNA with the same affinity as unacetylated Tat, but formation of a Tat-TAR-CyclinT1 ternary complex was completely inhibited in the presence of AcTat. We propose that Tat acetylation may help in dissociating the Tat cofactor CyclinT1 from TAR RNA and serve to transfer Tat onto the elongating RNA polymerase II

EphB–ephrin-B2 interactions are required for thymus migration during organogenesis

Thymus organogenesis requires coordinated interactions of multiple cell types, including neural crest (NC) cells, to orchestrate the formation, separation, and subsequent migration of the developing thymus from the third pharyngeal pouch to the thoracic cavity. The molecular mechanisms driving these processes are unclear; however, NC-derived mesenchyme has been shown to play an important role. Here, we show that, in the absence of ephrin-B2 expression on thymic NC-derived mesenchyme, the thymus remains in the cervical area instead of migrating into the thoracic cavity. Analysis of individual NC-derived thymic mesenchymal cells shows that, in the absence of ephrin-B2, their motility is impaired as a result of defective EphB receptor signaling. This implies a NC-derived cell-specific role of EphB–ephrin-B2 interactions in the collective migration of the thymic rudiment during organogenesis

Thymus Ontogeny and Development

The thymus is a primary lymphoid organ constituted by a 3D epithelial network that provides a specialized microenvironment in which seeding lymphoid progenitors undergo phenotypical and functional maturation. During the earlier steps of thymic organogenesis, the specification of the pharyngeal endoderm to thymus fate takes place independently of the expression of the transcription factor Foxn1 that, however, governs the later organogenesis of thymus together with the colonizing lymphoid cells. In the present chapter, we will review evidence describing early development of thymus and its resemblance with the development of endoderm-derived epithelial organs based on tubulogenesis and branching morphogenesis as well as the molecules known to be involved in these processes