A critical question in developmental biology is how complex programs of gene expression are orchestrated by a class of regulators known as selector genes. Selector genes code for transcription factors that autonomously govern the fates of groups of cells related to each other by virtue of their cell type, position or affiliation to an organ (1). For example, the FoxA transcription factor PHA-4 dictates the identity of cells within the C. elegans pharynx. Embryos that lack pha-4
fail to generate pharyngeal cells, and these cells acquire an alternative ectodermal fate instead (2,3). PHA-4 functions in combination with additional transcription factors to modulate genes at distinct stages and in different cell types during pharyngeal development (4,5). Here we explore the role of PHA-4 during transcriptional regulation. We identified components of the TIP60/SWR1 complex in a screen for loci that interact genetically with PHA-4. The predicted histone acetyltransferase mys-1
and chromatin remodeling factor ssl-1
each enhanced partial loss of pha-4
activity. In other organisms, the SSL-1 complex exchanges nucleosomes with histone H2A for those containing the variant H2Az (6). Nucleosomes containing H2Az appear less stable than those carrying H2A, which may facilitate the subsequent removal of nucleosomes for activation or repression (7). Consistent with this idea, C. elegans H2Az enhances the pharyngeal phenotype of pha-4
alleles, similar to ssl-1
. Furthermore, we observe H2Az associated with PHA-4 target promoters in nascent pharyngeal cells. We propose that the MYS-1/SSL-1 chromatin remodeling complex functions with PHA-4 to endow cells with pharyngeal competence by restructuring the chromatin environment around PHA-4 target genes. Chromatin restructuring may render these promoters susceptible to binding by additional transcription factors that modulate pharyngeal gene expression in conjunction with PHA-4.1) R. S. Mann, S. B. Carroll, Curr. Opin. Genet. Dev. 12, 592 (2002). 2) S. E. Mango, E. J. Lambie, J. Kimble, Development 120, 3019 (1994). 3) M. A. Horner et al., Genes Dev. 12, 1947 (1998). 4) J. Gaudet, S. Muttumu, M. Horner, S. E. Mango, PLoS Biol. 2, e352
(2004). 5) W. Ao, J. Gaudet, W. J. Kent, S. Muttumu, S. E. Mango, Science 305, 1743 (2004). 6) G. Mizuguchi, X. Shen, J. Landry, W. H. Wu, S. Sen, C. Wu, Science 303, 343 (2004). 7) D. W. Abbott, V. S. Ivanova, X Wang, W. M. Bonner, J. Ausio, J. Biol. Chem. 276, 945 (2001).