Morales Violette, Regnard Catherine, Izzo Annalisa, Vetter Irene, Becker Peter B
Adolf-Butenandt-Institut, Molekularbiologie, Schillerstr. 44, 80336 München, Germany.
Mol Cell Biol. 2005 Jul;25(14):5947-54. doi: 10.1128/MCB.25.14.5947-5954.2005.
The male-specific-lethal (MSL) proteins in Drosophila melanogaster serve to adjust gene expression levels in male flies containing a single X chromosome to equal those in females with a double dose of X-linked genes. Together with noncoding roX RNA, MSL proteins form the "dosage compensation complex" (DCC), which interacts selectively with the X chromosome to restrict the transcription-activating histone H4 acetyltransferase MOF (males-absent-on-the-first) to that chromosome. We showed previously that MSL3 is essential for the activation of MOF's nucleosomal histone acetyltransferase activity within an MSL1-MOF complex. By characterizing the MSL3 domain structure and its associated functions, we now found that the nucleic acid binding determinants reside in the N terminus of MSL3, well separable from the C-terminal MRG signatures that form an integrated domain required for MSL1 interaction. Interaction with MSL1 mediates the activation of MOF in vitro and the targeting of MSL3 to the X-chromosomal territory in vivo. An N-terminal truncation that lacks the chromo-related domain and all nucleic acid binding activity is able to trigger de novo assembly of the DCC and establishment of an acetylated X-chromosome territory.
果蝇中的雄性特异性致死（MSL）蛋白用于调节含有单条X染色体的雄蝇中的基因表达水平，使其与具有双倍剂量X连锁基因的雌蝇中的基因表达水平相等。MSL蛋白与非编码roX RNA一起形成“剂量补偿复合物”（DCC），该复合物与X染色体选择性相互作用，将转录激活组蛋白H4乙酰转移酶MOF（首条染色体上缺失雄性）限制在该染色体上。我们之前表明，MSL3对于在MSL1-MOF复合物中激活MOF的核小体组蛋白乙酰转移酶活性至关重要。通过表征MSL3的结构域结构及其相关功能，我们现在发现核酸结合决定簇位于MSL3的N端，与形成MSL1相互作用所需的整合结构域的C端MRG特征可明显分开。与MSL1的相互作用在体外介导MOF的激活，并在体内介导MSL3靶向X染色体区域。缺少染色体相关结构域和所有核酸结合活性的N端截短能够触发DCC的从头组装和乙酰化X染色体区域的建立。
