The Drosophila snr1 and brm proteins are related to yeast SWI/SNF proteins and are components of a large protein complex.

Abstract

During most of Drosophila development the regulation of homeotic gene transcription is controlled by two groups of regulatory genes, the trithorax group of activators and the Polycomb group of repressors. brahma (brm), a member of the trithorax group, encodes a protein related to the yeast SWI2/SNF2 protein, a subunit of a protein complex that assists sequence-specific activator proteins by alleviating the repressive effects of chromatin. To learn more about the molecular mechanisms underlying the regulation of homeotic gene transcription, we have investigated whether a similar complex exists in flies. We identified the Drosophila snr1 gene, a potential homologue of the yeast SNF5 gene that encodes a subunit of the yeast SWI/SNF complex. The snr1 gene is essential and genetically interacts with brm and trithorax (trx), suggesting cooperation in regulating homeotic gene transcription. The spatial and temporal patterns of expression of snr1 are similar to those of brm. The snr1 and brm proteins are present in a large (> 2 x 10(6) Da) complex, and they co-immunoprecipitate from Drosophila extracts. These findings provide direct evidence for conservation of the SWI/SNF complex in higher eucaryotes and suggest that the Drosophila brm/snr1 complex plays an important role in maintaining homeotic gene transcription during development by counteracting the repressive effects of chromatin.

HRX Leukemic Fusion Proteins Form a Heterocomplex with the Leukemia-associated Protein SET and Protein Phosphatase 2A

“…Studies in Drosophila have shown that Trx genetically opposes the action of the Polycomb group proteins that are thought to inactivate transcription through a mechanism involving modification of chromatin structure analogous to heterochromatin formation. In addition, one of the trx group members that may actually interact with Trx is Brahma, a Drosophila homologue of the yeast SWI/SNF2 protein, a component of the SWI/SNF ATP-dependent chromatin remodeling complex (61)(62)(63). Two other features of HRX are also consistent with overcoming the inhibitory effects of nucleosomes.…”

When the SWI/SNF complex remodels … the cell cycle

“…It was initially isolated in a screen for dominant suppressors of Polycomb mutations (Tamkun et al, 1992). Subsequent biochemical studies showed that the protein is associated with a complex very similar to the yeast SWI/SNF complex, containing at least six subunits related to SWI/SNF subunits (Dingwall et al, 1995;Papoulas et al, 1998). Another SWI2/SNF2-related protein, known as ISWI, has been found associated with di erent chromatin remodeling complexes (Ito et al, 1997;Tsukiyama and Wu, 1995;Varga-Weisz et al, 1995).…”

“…It also contains the Polybromo protein that is not present in the BAF complex. Polybromo, also called BAF180, contains six successive Bromodomains and shares some homology with three subunits of the yeast RSC complex, Rsc1, Rsc2 and Rsc4, both within and (Papoulas et al, 1998), 2 (Kwon et al, 1994;Nie et al, 2000), 3 (Kwon et al, 1994;Xue et al, 2000), 4 (Underhill et al, 2000), 5 (Du et al, 1998;Tsuchiya et al, 1998), 6 (Tamkun et al, 1992), 7 (Chiba et al, 1994;Khavari et al, 1993;Muchardt and Yaniv, 1993), 8 (Cao et al, 1997), 9 (Dingwall et al, 1995), 10 (Kalpana et al, 1994;Muchardt et al, 1995), 11 (Kal et al, 2000), 12 , 13 (Zhao et al, 1998), 14 (Cairns et al, 1999), 15 ¯anking the Bromodomains (Cairns et al, 1999;Callebaut et al, 1999). The presence of Polybromo in the PBAF complex suggests that PBAF may in fact correspond to the yeast RSC complex.…”

The SWI/SNF complex and cancer

“…Three other Drosophila trithorax genes have been identified as SWI/SNF homologs, which, in Drosophila, are known as BRM-associated proteins or BAPs: SNR1/BAP45 is homologous to the mammalian BAF47 and to yeast SNF5 (Dingwall et al, 1995); Osa is homologous to the mammalian BAF250 and to yeast SWI1 (Collins et al, 1999;Nie et al, 2000); and Moira/ BAP155 is homologous to the mammalian BAF155/ BAF170 and to the yeast SWI3 (Neely and Workman, 2002) (Table 1). Elucidation of the role of these genes in pattern formation established a functional link between SWI/SNF activity and development in multicellular organisms.…”