Beall Eileen L, Lewis Peter W, Bell Maren, Rocha Michael, Jones D Leanne, Botchan Michael R
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA.
Genes Dev. 2007 Apr 15;21(8):904-19. doi: 10.1101/gad.1516607. Epub 2007 Apr 2.
The Drosophila Myb-Muv B (MMB)/dREAM complex regulates gene expression and DNA replication site-specifically, but its activities in vivo have not been thoroughly explored. In ovarian amplification-stage follicle cell nuclei, the largest subunit, Mip130, is a negative regulator of replication, whereas another subunit, Myb, is a positive regulator. Here, we identified a mutation in mip40 and generated a mutation in mip120, two additional MMB subunits. Both mutants were viable, but mip120 mutants had many complex phenotypes including shortened longevity and severe eye defects. mip40 mutant females had severely reduced fertility, whereas mip120 mutant females were sterile, substantiating ovarian regulatory role(s) for MMB. Myb accumulation and binding to polytene chromosomes was dependent on the core factors of the MMB complex. In contrast to the documented mip130 mutant phenotypes, both mip40 and mip120 mutant males were sterile. We purified Mip40-containing complexes from testis nuclear extracts and identified tMAC, a new testis-specific meiotic arrest complex that contained Mip40, Caf1/p55, the Mip130 family member, Always early (Aly), and a Mip120 family member, Tombola (Tomb). Together, these data demonstrate that MMB serves diverse roles in different developmental pathways, and members of MMB can be found in alternative, noninteracting complexes in different cell types.
果蝇Myb-Muv B(MMB)/dREAM复合物特异性地调节基因表达和DNA复制,但其在体内的活性尚未得到充分研究。在卵巢扩增期卵泡细胞核中,最大的亚基Mip130是复制的负调节因子,而另一个亚基Myb是正调节因子。在这里,我们鉴定了mip40中的一个突变,并在另外两个MMB亚基mip120中产生了一个突变。两个突变体都是可行的,但mip120突变体有许多复杂的表型,包括寿命缩短和严重的眼睛缺陷。mip40突变体雌性的生育力严重降低,而mip120突变体雌性不育,证实了MMB在卵巢中的调节作用。Myb的积累和与多线染色体的结合依赖于MMB复合物的核心因子。与已记录的mip130突变体表型相反,mip40和mip120突变体雄性都是不育的。我们从睾丸核提取物中纯化了含有Mip40的复合物,并鉴定了tMAC,一种新的睾丸特异性减数分裂阻滞复合物,它包含Mip40、Caf1/p55、Mip130家族成员Always early(Aly)和Mip120家族成员Tombola(Tomb)。总之,这些数据表明MMB在不同的发育途径中发挥着不同的作用,并且MMB的成员可以在不同细胞类型中的替代、非相互作用复合物中找到。