García-Oliver Encar, Ramus Claire, Perot Jonathan, Arlotto Marie, Champleboux Morgane, Mietton Flore, Battail Christophe, Boland Anne, Deleuze Jean-François, Ferro Myriam, Couté Yohann, Govin Jérôme
U1038, Université Grenoble Alpes, Institut de Biosciences et Biotechnologies de Grenoble (BIG), Grenoble, France.
Laboratoire Biologie à Grande Echelle (BGE), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Biosciences et Biotechnologies de Grenoble (BIG), Grenoble, France.
PLoS Genet. 2017 Jan 9;13(1):e1006541. doi: 10.1371/journal.pgen.1006541. eCollection 2017 Jan.
Bromodomain and Extra-terminal motif (BET) proteins play a central role in transcription regulation and chromatin signalling pathways. They are present in unicellular eukaryotes and in this study, the role of the BET protein Bdf1 has been explored in Saccharomyces cerevisiae. Mutation of Bdf1 bromodomains revealed defects on both the formation of spores and the meiotic progression, blocking cells at the exit from prophase, before the first meiotic division. This phenotype is associated with a massive deregulation of the transcription of meiotic genes and Bdf1 bromodomains are required for appropriate expression of the key meiotic transcription factor NDT80 and almost all the Ndt80-inducible genes, including APC complex components. Bdf1 notably accumulates on the promoter of Ndt80 and its recruitment is dependent on Bdf1 bromodomains. In addition, the ectopic expression of NDT80 during meiosis partially bypasses this dependency. Finally, purification of Bdf1 partners identified two independent complexes with Bdf2 or the SWR complex, neither of which was required to complete sporulation. Taken together, our results unveil a new role for Bdf1 -working independently from its predominant protein partners Bdf2 and the SWR1 complex-as a regulator of meiosis-specific genes.
溴结构域和额外末端基序(BET)蛋白在转录调控和染色质信号通路中发挥核心作用。它们存在于单细胞真核生物中,在本研究中,已在酿酒酵母中探索了BET蛋白Bdf1的作用。Bdf1溴结构域的突变揭示了孢子形成和减数分裂进程方面的缺陷,使细胞在第一次减数分裂前的前期退出时受阻。这种表型与减数分裂基因转录的大量失调有关,Bdf1溴结构域是关键减数分裂转录因子NDT80以及几乎所有Ndt80诱导基因(包括APC复合体成分)适当表达所必需的。Bdf1特别在Ndt80的启动子上积累,其募集依赖于Bdf1溴结构域。此外,减数分裂期间NDT80的异位表达部分绕过了这种依赖性。最后,Bdf1伴侣的纯化鉴定出与Bdf2或SWR复合体形成的两个独立复合体,完成孢子形成均不需要它们。综上所述,我们的结果揭示了Bdf1的一个新作用——独立于其主要蛋白伴侣Bdf2和SWR1复合体发挥作用——作为减数分裂特异性基因的调节因子。