Vanoosthuyse Vincent, Legros Pénélope, van der Sar Sjaak J A, Yvert Gaël, Toda Kenji, Le Bihan Thierry, Watanabe Yoshinori, Hardwick Kevin, Bernard Pascal
CNRS, UMR5239, LBMC; Ecole Normale Supérieure de Lyon; Université Lyon 01, Lyon, France; Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, United Kingdom.
CNRS, UMR5239, LBMC; Ecole Normale Supérieure de Lyon; Université Lyon 01, Lyon, France.
PLoS Genet. 2014 Jun 19;10(6):e1004415. doi: 10.1371/journal.pgen.1004415. eCollection 2014 Jun.
Functional links connecting gene transcription and condensin-mediated chromosome condensation have been established in species ranging from prokaryotes to vertebrates. However, the exact nature of these links remains misunderstood. Here we show in fission yeast that the 3' end RNA processing factor Swd2.2, a component of the Cleavage and Polyadenylation Factor (CPF), is a negative regulator of condensin-mediated chromosome condensation. Lack of Swd2.2 does not affect the assembly of the CPF but reduces its association with chromatin. This causes only limited, context-dependent effects on gene expression and transcription termination. However, CPF-associated Swd2.2 is required for the association of Protein Phosphatase 1 PP1(Dis2) with chromatin, through an interaction with Ppn1, a protein that we identify as the fission yeast homologue of vertebrate PNUTS. We demonstrate that Swd2.2, Ppn1 and PP1Dis2 form an independent module within the CPF, which provides an essential function in the absence of the CPF-associated Ssu72 phosphatase. We show that Ppn1 and Ssu72, like Swd2.2, are also negative regulators of condensin-mediated chromosome condensation. We conclude that Swd2.2 opposes condensin-mediated chromosome condensation by facilitating the function of the two CPF-associated phosphatases PP1 and Ssu72.
从原核生物到脊椎动物等多种物种中，已建立起连接基因转录与凝聚素介导的染色体凝聚的功能联系。然而，这些联系的确切性质仍未得到充分理解。在此，我们在裂殖酵母中表明，3' 端RNA加工因子Swd2.2（切割与聚腺苷酸化因子（CPF）的一个组分）是凝聚素介导的染色体凝聚的负调控因子。缺乏Swd2.2并不影响CPF的组装，但会减少其与染色质的结合。这仅对基因表达和转录终止产生有限的、依赖于上下文的影响。然而，CPF相关的Swd2.2通过与Ppn1相互作用，对于蛋白磷酸酶1（PP1，Dis2）与染色质的结合是必需的，我们将Ppn1鉴定为脊椎动物PNUTS的裂殖酵母同源物。我们证明，Swd2.2、Ppn1和PP1Dis2在CPF内形成一个独立模块，在缺乏与CPF相关的Ssu72磷酸酶时提供一项基本功能。我们表明，Ppn1和Ssu72与Swd2.2一样，也是凝聚素介导的染色体凝聚的负调控因子。我们得出结论，Swd2.2通过促进两种与CPF相关的磷酸酶PP1和Ssu72的功能来对抗凝聚素介导的染色体凝聚。
