A histone deacetylase adjusts transcription kinetics at coding sequences during Candida albicans morphogenesis.
A histone deacetylase adjusts transcription kinetics at coding sequences during Candida albicans morphogenesis.
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DOI：
10.1371/journal.pgen.1003118
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发表时间：
2012
期刊：
影响因子：
4.5
通讯作者：
Kuchler K
中科院分区：
文献类型：
--
作者：
Hnisz D;Bardet AF;Nobile CJ;Petryshyn A;Glaser W;Schöck U;Stark A;Kuchler K
尽管它们作为转录抑制物的经典作用，但几种组蛋白脱乙酰酶，包括面包酵母Set 3/Hos 2复合物（Set 3C），促进基因表达。在双态人类病原体白色念珠菌中，Set 3C的同源物抑制酵母到丝状体的转变，但这种功能的精确分子细节仍然难以捉摸。在这里，我们使用ChIP-Seq和RNA-Seq的组合来显示Set 3C作为C中代谢和形态发生相关基因的转录辅因子。白色念珠菌Set 3C的结合与真菌形态发生过程中的基因表达相关;然而，令人惊讶的是，SET 3的缺失使大多数基因的稳态表达水平不变，无论是在指数酵母生长期还是在酵母-丝状体转变期。精细的时间分辨率的转录在经历这种转变的细胞显示，Set 3C调制关键形态发生相关基因的瞬时表达变化。这些包括由NRG 1、EFG 1、BRG 1和TEC 1组成的转录因子簇，其形成控制菌丝分化的调节回路。Set 3C似乎通过调节转录动力学来限制这些因子，并且SET 3缺陷细胞的超丝状表型可以通过突变回路因子来逆转。这些结果表明，在编码区的染色质状态代表了一个动态的平台，影响转录动力学。此外，我们认为，在编码序列的转录可以暂时解耦的潜在冲突的启动子信息在动态环境中。许多人类病原真菌能够改变它们的形态学特性，包括它们的大小和形状，以响应它们的外部环境。这种能力是感染的关键，在分子水平上还没有完全理解。我们以前已经表明，不仅是DNA结合转录因子，而且染色质修饰酶与DNA结合蛋白相互作用，是重要的调节模式真菌C的形态发生。白色念珠菌在这项工作中，我们解剖这样的染色质修饰酶调节真菌形态发生。我们惊奇地发现，染色质的扰动对稳态转录的影响很小，但在分化的C.白色念珠菌细胞改变的转录动力学影响一组决定形态的转录因子基因。因此，我们确定了一个染色质修饰剂，发挥动力学控制转录因子基因控制真菌形态发生。结果突出了染色质的重要性，以确定转录变化的动力学，而不是稳态转录水平。
Despite their classical role as transcriptional repressors, several histone deacetylases, including the baker's yeast Set3/Hos2 complex (Set3C), facilitate gene expression. In the dimorphic human pathogen Candida albicans, the homologue of the Set3C inhibits the yeast-to-filament transition, but the precise molecular details of this function have remained elusive. Here, we use a combination of ChIP–Seq and RNA–Seq to show that the Set3C acts as a transcriptional co-factor of metabolic and morphogenesis-related genes in C. albicans. Binding of the Set3C correlates with gene expression during fungal morphogenesis; yet, surprisingly, deletion of SET3 leaves the steady-state expression level of most genes unchanged, both during exponential yeast-phase growth and during the yeast-filament transition. Fine temporal resolution of transcription in cells undergoing this transition revealed that the Set3C modulates transient expression changes of key morphogenesis-related genes. These include a transcription factor cluster comprising of NRG1, EFG1, BRG1, and TEC1, which form a regulatory circuit controlling hyphal differentiation. Set3C appears to restrict the factors by modulating their transcription kinetics, and the hyperfilamentous phenotype of SET3-deficient cells can be reverted by mutating the circuit factors. These results indicate that the chromatin status at coding regions represents a dynamic platform influencing transcription kinetics. Moreover, we suggest that transcription at the coding sequence can be transiently decoupled from potentially conflicting promoter information in dynamic environments. Many human pathogenic fungi are able to change their morphological properties, including their size and shape, in response to their outside environment. This ability, which is key for infection, is not completely understood on the molecular level. We have previously shown that not just DNA–binding transcription factors, but also chromatin-modifying enzymes that interact with DNA–binding proteins, are important regulators of morphogenesis in the model fungus C. albicans. In this work we dissect how such a chromatin-modifying enzyme regulates fungal morphogenesis. We surprisingly found that perturbation of chromatin has little influence on steady-state transcription, but modulates transient gene expression changes in differentiating C. albicans cells. Altered transcription kinetics affects a group of transcription factor genes that determine morphology. We thus identified a chromatin modifier that exerts kinetic control of transcription factor genes to control fungal morphogenesis. The results highlight the importance of chromatin to determine the kinetics of transcription changes rather than the steady-state transcript levels.
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DOI：
10.1073/pnas.0912427107
发表时间：
2010-01-26
影响因子：
11.1
作者：
da Rosa, Jessica Lopes;Boyartchuk, Victor L.;Kaufman, Paul D.
通讯作者：
Kaufman, Paul D.
影响因子：
64.5
作者：
Lee JS;Smith E;Shilatifard A
通讯作者：
Shilatifard A
影响因子：
3.6
作者：
Frohner IE;Bourgeois C;Yatsyk K;Majer O;Kuchler K
通讯作者：
Kuchler K
影响因子：
9.8
作者：
Lavoie H;Hogues H;Mallick J;Sellam A;Nantel A;Whiteway M
通讯作者：
Whiteway M
影响因子：
4.5
作者：
Homann OR;Dea J;Noble SM;Johnson AD
通讯作者：
Johnson AD