Reevaluating the function of a transcription factor: MBF-1 as a sea urchin chromatin organizer ?

The Zinc-finger MBF-1 factor is involved in the expression of the early histone genes during devel-opment of the sea urchin embryo (1, 2). In spite of being a transcription activator, the DNA-binding domain of MBF-1 shares high sequence similarity with that of the chromatin organizer CTCF of vertebrates and drosophila (3). On the other hand, extensive in silico analysis failed to identify the sea urchin CTCF ortholog (4). This led us to speculate that MBF-1 somehow could have co-opted the function of CTCF during evolution of the echinoderms. Since in vertebrates CTCF binds Hox chromatin, to support our hypothesis, we first identified high-score putative binding sequences for CTCF/MBF-1 with…

Integrated computational and experimental approaches for the identification of new molecules with readthrough activity on premature termination codons (PTCs) in cystic fibrosis cells

Novel molecules for the readthrough of PTCs in biological model systems and in cystic fibrosis cells

Optimization of a new lead promoting the readthrough of the nonsense mutations for CFTR rescue in human CF cells

Optimization of a new lead promoting the readthrough of the nonsense mutations for CFTR rescue in human CF cells Laura Lentini, Raffaella Melfi, Sara Baldassano, Marco Tutone, Aldo Di Leonardo, Andrea Pace, Ivana Pibiri Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo Background and rationale Cystic Fibrosis patients with nonsense mutations in the CFTR gene have a more severe form of the disease. Nonsense mutations represent about 10% of the mutations that affect the CFTR gene and they are frequently associated to the classical F508 mutation (1). A potential treatment for this genetic alteration is to promote the translationa…

Homeobox genes and sea urchin development.

We describe the expression of three Paracentrotus lividus homeobox-containing genes of the dispersed class during sea urchin embryogenesis and discuss their possible roles in the mechanisms of cell specification and embryo morphogenesis. PIHbox12 represents the first regulator identified in sea urchin that belongs to the zygotic class of transcription factors. Its early and transient expression and the localization of transcripts suggests that PIHbox12 is involved in cell fate specification of the oral or aboral ectodermal territories at the early cleavage stages. PIHbox9 is expressed just after the completion of gastrulation in a narrow stripe of cells at the ectoderm-endoderm boundary. It…

Translational Readthrough Inducing Drugs (TRIDs): a study of biodistribution evaluation in mice models