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The SAGA complex provides a paradigm for multisubunit histone modifying complexes. Although first characterized as a histone acetyltransferase, because of the Gcn5 subunit, SAGA is now known to contain a second activity, a histone deubiquitinase, as well as subunits important for interactions with transcriptional activators and the general transcription machinery. The functions of SAGA in transcriptional activation are well-established in Saccharomyces cerevisiae. Recent studies in S. pombe, Drosophila, and mammalian systems reveal that SAGA also has important roles in transcript elongation, the regulation of protein stability, and telomere maintenance. These functions are essential for normal embryo development in flies and mice, and mutations or altered expression of SAGA subunits correlate with neurological disease and aggressive cancers in humans. [Copyright &y& Elsevier]

A wealth of biochemical and cellular data, accumulated over several years by multiple groups, has provided a great degree of insight into the molecular mechanisms of actions of GCN5 and PCAF in gene activation. Studies of these lysine acetyltransferases (KATs) in vitro , in cultured cells, have revealed general mechanisms for their recruitment by sequence-specific binding factors and their molecular functions as transcriptional co-activators. Genetic studies indicate that GCN5 and PCAF are involved in multiple developmental processes in vertebrates, yet our understanding of their molecular functions in these contexts remains somewhat rudimentary. Understanding the functions of GCN5/PCAF in developmental processes provides clues to the roles of these KATs in disease states. Here we will review what is currently known about the developmental roles of GCN5 and PCAF, as well as emerging role of these KATs in oncogenesis. • Gcn5 null embryos are defective in somitogenesis and neurulation, whereas Pcaf null mice show a complete lack of developmental phenotypes. • Hypomorphic mutations that lower Gcn5 levels or abrogate KAT function result in developmental defects such as skeleton defects and exencephaly. • GCN5 is preferably recruited to Myc and E2F1 binding motifs in embryonic stem cells, and multiple Myc and E2F1 targets are affected by Gcn5 loss. • Gcn5 and Pcaf play important roles in both the innate and adaptive immune systems. • GCN5/PCAF KAT activity is linked with the survival of human cancer cell types, however, no clinically useful inhibitor of GCN5/PCAF exist to date. [ABSTRACT FROM AUTHOR]

The Drosophila neuralized (neur) gene belongs to the neurogenic group of genes involved in regulating cell–cell interactions required for neural precursor development. neur mutant phenotypes include strong overcommitment to neural fates at the expense of epidermal fates. The human neuralized homolog (NEURL) has been recently determined and found to map to chromosome 10q25.1 within the region frequently deleted in malignant astrocytomas. Because of its potential importance in developmental processes, we analyzed the structure of the mouse homolog, Neurl, and its expression pattern in embryonic tissues. Neurl activity is detected from early developmental stages in several tissues and organs including neural tissues, limbs, the skeletal system, sense organs and internal organs undergoing epithelial–mesenchymal interactions. Neurl encodes a polypeptide associated with the plasma membrane but also detected in the cytoplasm. Similarly to the Drosophila gene, mammalian neuralized may code for an important regulatory factor. [Copyright &y& Elsevier]