• 19 Apr 07
  

  marquis
  • Using a quantitative chromatin localization assay [6], we find that the transcriptional activation of both INO1 and GAL1 genes in yeast is biphasic, with the mRNA levels increasing dramatically after gene recruitment is complete. RNA polymerase II activity was not required for peripheral recruitment of INO1. Furthermore, when cells were shifted from activating to repressing conditions, INO1 and GAL1 remained localized at the nuclear periphery for generations. We find that localization at the periphery defines a distinct, heritable state that marks recently repressed genes and promotes reactivation. The reactivation of GAL1 was more rapid in cells that had previously activated the gene, even after six generations of repression. The rate of activation of INO1 was accelerated when the gene was artificially tethered to the nuclear envelope and was delayed in a mutant blocked for gene recruitment.
  • In contrast, recruitment of genes to the nuclear periphery has also been suggested to reflect coupling between transcription and mRNA export. Chromatin immunoprecipitation studies suggest that the interaction of mating pheromone–induced genes with the NPC is mediated by the mRNA [12].
  • Live-cell four-dimensional imaging experiments reveal that recruitment is associated with both a change in the subnuclear distribution of genes and a reduction in their mobility, resulting in constrained movement near the nuclear envelope [9,14].
  • The subnuclear localization of DNA has important roles in regulating transcription [1,2]. In particular, localization of chromatin near the nuclear periphery has well-documented effects on transcription.

  • H2A.Z-Mediated Localization of Genes at the Nuclear Periphery Confers Epigenetic Memory of Previous Transcriptional State

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      Donna Garvey Brickner, Ivelisse Cajigas, Yvonne Fondufe-Mittendorf, Sara Ahmed, Pei-Chih Lee, Jonathan Widom, Jason H. Brickner^* 

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      1 Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, Illinois, United States of America 

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    Many genes are recruited to the nuclear periphery upon transcriptional activation. The mechanism and functional significance of this recruitment is unclear. We find that recruitment of the yeast INO1 and GAL1 genes to the nuclear periphery is rapid and independent of transcription. Surprisingly, these genes remain at the periphery for generations after they are repressed. Localization at the nuclear periphery serves as a form of memory of recent transcriptional activation, promoting reactivation. Previously expressed GAL1 at the nuclear periphery is activated much more rapidly than long-term repressed GAL1 in the nucleoplasm, even after six generations of repression. Localization of INO1 at the nuclear periphery is necessary and sufficient to promote more rapid activation. This form of transcriptional memory is chromatin based; the histone variant H2A.Z is incorporated into nucleosomes within the recently repressed INO1 promoter and is specifically required for rapid reactivation of both INO1 and GAL1. Furthermore, H2A.Z is required to retain INO1 at the nuclear periphery after repression. Therefore, H2A.Z-mediated localization of recently repressed genes at the nuclear periphery represents an epigenetic state that confers memory of transcriptional activation and promotes reactivation.

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