H2A.Z-mediated localization of genes at the nuclear periphery confers epigenetic memory of previous transcriptional state.
H2A.Z-mediated localization of genes at the nuclear periphery confers epigenetic memory of previous transcriptional state.
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DOI：
10.1371/journal.pbio.0050081
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发表时间：
2007-04
期刊：
影响因子：
9.8
通讯作者：
Brickner JH
中科院分区：
文献类型：
--
作者：
Brickner DG;Cajigas I;Fondufe-Mittendorf Y;Ahmed S;Lee PC;Widom J;Brickner JH
许多基因在转录激活后被募集到核外围。这种招募的机制和功能意义尚不清楚。我们发现，酵母INO 1和GAL 1基因的核周边的招聘是快速和独立的转录。令人惊讶的是，这些基因在被抑制后仍然存在于边缘几代人。定位在核周边作为一种形式的记忆最近的转录激活，促进再激活。以前表达的GAL 1在核周边被激活更迅速地比长期压抑的GAL 1在核质，即使经过六代的镇压。INO 1在核周边的定位是必要的，足以促进更快的激活。这种形式的转录记忆是基于染色质的;组蛋白变体H2A.Z被整合到最近被抑制的INO 1启动子内的核小体中，并且是INO 1和GAL 1快速重新激活所特别需要的。此外，H2A.Z需要在阻遏后将INO 1保留在核周边。因此，H2 A. Z介导的最近被抑制的基因在核周边的定位代表了赋予转录激活记忆并促进再激活的表观遗传状态。真核细胞控制着染色体的空间排列，基因的定位可以反映并影响其转录状态。简单真核生物酿酒酵母中的许多基因在表达时通过与核孔复合体的相互作用被“招募”到核外围。外周募集的功能意义尚不清楚。在这里，我们表明，募集的基因积极保留在转录被抑制后的几代人的外围。这表明，在核周边的本地化代表了一种新的遗传状态，可能允许简单的真核生物“记住”以前的转录激活。这种类型的记忆允许更强大的基因重新激活，这表明它是适应性的。最后，保留在核周边和快速再活化都需要组蛋白H2 A的变体形式。适应性记忆不同于其他类型的转录记忆。在发育记忆中，在胚胎发生早期由转录调控因子建立的转录状态在这些调控因子消失后很长时间内得以传播。适应性记忆并不传播一种状态，而是代表一种作为信息源的新状态。通过这种方式，它类似于细胞学习的基本形式，允许细胞从最近的经验中受益。将活性基因募集到酵母细胞核的外围不需要同时转录。
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. Eukaryotic cells control the spatial arrangement of chromosomes; the localization of genes can both reflect and contribute to their transcriptional state. A number of genes in the simple eukaryote brewer's yeast are “recruited” to the nuclear periphery through interactions with the nuclear pore complex when they are expressed. The functional significance of peripheral recruitment is unclear. Here, we show that recruited genes are actively retained at the periphery for generations after transcription is repressed. This suggests that localization at the nuclear periphery represents a novel inherited state that might allow simple eukaryotic organisms to “remember” previous transcriptional activation. This type of memory allows for more robust reactivation of genes, suggesting that it is adaptive. Finally, both retention at the nuclear periphery and rapid reactivation require a variant form of histone H2A. Adaptive memory is distinct from other types of transcriptional memory. In developmental memory, transcriptional states established by transcriptional regulators early in embryogenesis are propagated long after these regulators have disappeared. Adaptive memory does not propagate a state, but represents a novel state that serves as a source of information. In this way, it resembles a rudimentary form of cellular learning that allows cells to benefit from recent experience. Recruitment of active genes to the periphery of the yeast nucleus does not require concurrent transcription.
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DOI：
10.1073/pnas.172403699
发表时间：
2002-12-10
影响因子：
11.1
作者：
Ahmad, K;Henikoff, S
通讯作者：
Henikoff, S
影响因子：
56.9
作者：
Loewen, CJR;Gaspar, ML;Levine, TP
通讯作者：
Levine, TP
影响因子：
11.4
作者：
Abruzzi, Katharine C.;Belostotsky, Dmitry A.;Rosbash, Michael
通讯作者：
Rosbash, Michael
DOI：
10.1165/ajrcmb/1.1.5
发表时间：
1989-07-01
影响因子：
6.4
作者：
DEAN, DC
通讯作者：
DEAN, DC
影响因子：
14.9
作者：
Jackson, JD;Gorovsky, MA
通讯作者：
Gorovsky, MA