title: Cytoskeletal proteins regulate chromatin access of BR-C transcription factor and Rpd3-Sin3A histone deacetylase complex in Drosophila salivary glands.
abstract: At the onset of Drosophila metamorphosis the steroid hormone ecdysone induces a process leading to a rapid degeneration of the larval salivary glands (SGs). Ecdysone acts through the ecdysone receptor heterodimer, which activates primary response genes. In particular these genes include the Broad-Complex (BR-C) gene encoding a set of BTB/POZ-transcription factors, among which the Z1 isoform is critical for SG cell death. The timing of SG disappearance depends upon of p127 (l(2)gl) , a cytoskeletal tumor suppressor that interacts with nonmuscle myosin II heavy chain (nmMHC) encoded by the zipper (zip) gene. Reduced l(2)gl expression delays SG histolysis whereas over-expression accelerates this process without affecting larval and pupal development. However, the mechanism by which l(2)gl controls SG histolysis remains yet unknown. Here we analyze the regulation controlled by p127 (l(2)gl)  and nmMHC in the cytoplasm on the association of BR-C Z1 with chromatin and remodeling factors, such as Rpd3, Sin3A, and Smrter. In wild-type SGs these factors bind to chromatin but in l(2)gl SGs they accumulate in the cytoplasm and the cortical nuclear zone (CNZ). Similar chromatin exclusion occurs in SGs of developmentally delayed zip (E(br)) /+ larvae or can be achieved by high levels of nmMHC synthesis. The present data show that p127 (l(2)gl)  and nmMHC regulate the access of BR-C Z1, Rpd3, Sin3A, and Smrter to chromatin. As the interaction between p127 (l(2)gl)  and nmMHC occurs in the cytoplasm, we propose that these nuclear factors are processed by p127 (l(2)gl)  and then released from p127 (l(2)gl)  by nmMHC to allow their binding to chromatin. This process may constitute a novel mechanism of gene regulation, which in the absence of p127 (l(2)gl) , or excessive amounts of nmMHC, could lead to a fixed configuration in the pattern of gene expression that prevents further progression of SG differentiation, and programmed cell death (PCD). Such a transcriptional block could play a critical role in the neoplastic transformation of l(2)gl tissues.
authors: Institute of Experimental Endocrinology, Slovak Academy of Sciences, Vlárska 3, 83306 Bratislava, Slovakia. ueenfark@savba.sk
authors: Robert
authors: R
authors: Farkaš
authors: Silvia
authors: S
authors: Kuchárová-Mahmood
authors: Lucia
authors: L
authors: Mentelová
authors: Pavel
authors: P
authors: Juda
authors: Ivan
authors: I
authors: Raška
authors: Bernard M
authors: BM
authors: Mechler
mesh_terms: D000818:Animals; D017209:Apoptosis; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D004330:Drosophila / Q000201:enzymology / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004440:Ecdysone / Q000378:metabolism; D056284:Histone Deacetylase 1 / Q000378:metabolism*; D007814:Larva; D024462:Myosin Type II / Q000378:metabolism; D011987:Receptors, Steroid / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D012469:Salivary Glands / Q000201:enzymology / Q000378:metabolism; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: C102117:Br protein, Drosophila; D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; D011987:Receptors, Steroid; D012097:Repressor Proteins; C099683:SIN3A transcription factor; D014157:Transcription Factors; C055469:ecdysone receptor; D004440:Ecdysone; C512966:HDAC1 protein, Drosophila; D056284:Histone Deacetylase 1; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D024462:Myosin Type II