The trithorax group gene brahma (brm) encodes the ATPase subunit of a chromatin-remodeling complex

Homeotic genes specify the identities of segments during development. Many of the homeotic genes in Drosophila are found in two clusters, the Antennapedia complex (ANTC) and the bithorax complex (BXC) (Duncan, 1987; Kaufman et al., 1990), and are also referred to collectively as the HOM genes. The homeotic genes were first identified because mutations in them cause cells to form structures characteristic of another part of the body. For example, mutations in the HOM gene Antennapedia (Antp) cause the antennal cells to differentiate leg structures. The proteins encoded by the HOM genes share a 60 amino acid DNA-binding motif, the homeodomain, and function as positive or negative transcription factors of target genes. Transcriptional regulation of the HOM genes is complex. The HOM genes have large cis-regulatory regions with redundant cis-regulatory elements (reviewed by Kennison, 1993). The establishment of individual HOM gene expression patterns early in embryogenesis is primarily controlled by the segmentation genes (for reviews see Ingham and Martínez Arias, 1992; Simon, 1995). However, many of the segmentation proteins disappear later in embryogenesis and other sets of genes are required to maintain the expression patterns of the HOM genes. Two groups of regulatory genes are required for maintenance of HOM gene expression. One group of genes, the Polycomb group (PcG), maintain repression of HOM genes. The second group of genes, the trithorax group (trxG), are positive regulatory factors required to maintain HOM gene expression (reviewed by Kennison, 1995; Simon, 1995). Many members of the trxG of genes were identified as suppressors of phenotypes caused by derepression of HOM genes (Kennison and Tamkun, 1988; Kennison and Tamkun, 1992). Because there are many expected regulatory steps involved in maintaining HOM gene function (such as transcriptional activation, posttranslational modification of HOM proteins, and expression of required HOM protein cofactors) the trxG genes are expected to be far more heterogeneous in function than the PcG genes, which all appear to repress transcription. Kennison and Tamkun (1988) identified a dozen new trxG genes among which brahma (brm) is the most understood. BRM is the Drosophila homologue of the yeast SWI2/SNF2 protein and the human BRG1 and HBRM proteins. The BRM and SWI2/SNF2 proteins are most highly related within four segments: a DNA-dependent ATPase domain, a bromodomain, and two domains of unknown function. The DNA-dependent ATPase domain and one of the two domains of unknown function have been shown to be essential for BRM function, but the bromodomain appears to be dispensable (Elfring et al., 1998). 733 Development 126, 733-742 (1999) Printed in Great Britain © The Company of Biologists Limited 1999 DEV5258