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

Abstract

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 within the single sea urchin Hox gene cluster. Moreover, we observed the full evolu-tionary conservation of these binding sites in S. purpuratus and P. lividus species. Worth of men-tion, by chromatin immunoprecipitation (ChIP) assay, we detected the occupancy of MBF-1 on hox11/13-a, -b, and -c regulatory sequences at distinct stages of development. As expected from the binding of an activator, we found that the association of MBF-1 to the cis-regulatory sequences of both hox11/13-a and -b genes relates to the transcriptional status of these genes. Strikingly, we also mapped the physical binding of MBF-1 to hox11/13-c, which is instead not expressed during em-bryogenesis. Altogether, these observations indeed suggest the possibility that MBF-1, besides be-ing a transcription activator, could also function as a general chromatin organizer. To further support this hypothesis, we are planning ChIP-seq experiments to identify the association of MBF-1 to the sea urchin chromatin at a genome-wide level. 1. Di Caro, V. et al. (2007) J. Mol. Bio.,365, 1285-97. 2. Cavalieri,V et al. (2009) Nucleic Acid Res, 37,7407-7415. 3. Heger , P. et al. (2012) PNAS, 109, 17507–17512. 4. Cavalieri, V. et al. (2013) Plos Genetics, 9, e1003847.