Functional antagonism between Sas3 and Gcn5 acetyltransferases and ISWI chromatin remodelers.
Functional antagonism between Sas3 and Gcn5 acetyltransferases and ISWI chromatin remodelers.
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DOI：
10.1371/journal.pgen.1002994
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发表时间：
2012
期刊：
影响因子：
4.5
通讯作者：
Pillus L
中科院分区：
文献类型：
--
作者：
Lafon A;Petty E;Pillus L
Chromatin-modifying enzymes and ATP-dependent remodeling complexes have been intensely studied individually, yet how these activities are coordinated to ensure essential cell functions such as transcription, replication, and repair of damage is not well understood. In this study, we show that the critical loss of Sas3 and Gcn5 acetyltransferases in yeast can be functionally rescued by inactivation of ISWI remodelers. This genetic interaction depends on the ATPase activities of Isw1 and Isw2, suggesting that it involves chromatin remodeling activities driven by the enzymes. Genetic dissection of the Isw1 complexes reveals that the antagonistic effects are mediated specifically by the Isw1a complex. Loss of Sas3 and Gcn5 correlates with defective RNA polymerase II (RNAPII) occupancy at actively transcribed genes, as well as a significant loss of H3K14 acetylation. Inactivation of the Isw1a complex in the acetyltransferase mutants restores RNAPII recruitment at active genes, indicating that transcriptional regulation may be the mechanism underlying suppression. Dosage studies and further genetic dissection reveal that the Isw1b complex may act in suppression through down-regulation of Isw1a. These studies highlight the importance of balanced chromatin modifying and remodeling activities for optimal transcription and cell growth. In eukaryotes, essential processes such as transcription, replication, and repair of damage occur in the context of chromatin. The structure of chromatin is tightly regulated during the cell cycle by chromatin-modifying enzymes, including acetyltransferases, and ATP-dependent remodeling complexes. Although there has been extensive characterization of their individual functions, little is known about how their activities are coordinated to maintain cell viability. In this study, we show that the critical loss of Sas3 and Gcn5 acetyltransferases can be functionally rescued by inactivation of ISWI remodelers. At a molecular level, the effects on cell viability tightly correlate with the recruitment of RNA polymerase II (RNAPII) at active genes, suggesting that transcriptional regulation may be the mechanism underlying cell viability rescue. Our genetic analyses reveal distinct roles for the two Isw1a and Isw1b complexes; in particular, the antagonistic effects are mediated specifically by the Isw1a complex. These studies highlight the importance of balanced chromatin modifying and remodeling activities for optimal transcription and cell growth.
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影响因子：
5.3
作者：
Gelbart, ME;Rechsteiner, T;Tsukiyama, T
通讯作者：
Tsukiyama, T
影响因子：
5.3
作者：
Gangaraju, Vamsi K.;Bartholomew, Blaine
通讯作者：
Bartholomew, Blaine
影响因子：
4.8
作者：
Grant, PA;Eberharter, A;Workman, JL
通讯作者：
Workman, JL
影响因子：
16
作者：
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通讯作者：
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影响因子：
7.7
作者：
Corona, DFV;Clapier, CR;Tamkun, JW
通讯作者：
Tamkun, JW