Dultz Elisa, Tjong Harianto, Weider Elodie, Herzog Mareike, Young Barry, Brune Christiane, Müllner Daniel, Loewen Christopher, Alber Frank, Weis Karsten
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720 Department of Biology, Institute of Biochemistry, Eidgenössische Technische Hochschule Zurich, 8093 Zurich, Switzerland
Department of Biological Sciences, Molecular and Computational Biology, University of Southern California, Los Angeles, CA 90089.
J Cell Biol. 2016 Feb 1;212(3):321-34. doi: 10.1083/jcb.201507069. Epub 2016 Jan 25.
The organization of the genome is nonrandom and important for correct function. Specifically, the nuclear envelope plays a critical role in gene regulation. It generally constitutes a repressive environment, but several genes, including the GAL locus in budding yeast, are recruited to the nuclear periphery on activation. Here, we combine imaging and computational modeling to ask how the association of a single gene locus with the nuclear envelope influences the surrounding chromosome architecture. Systematic analysis of an entire yeast chromosome establishes that peripheral recruitment of the GAL locus is part of a large-scale rearrangement that shifts many chromosomal regions closer to the nuclear envelope. This process is likely caused by the presence of several independent anchoring points. To identify novel factors required for peripheral anchoring, we performed a genome-wide screen and demonstrated that the histone acetyltransferase SAGA and the activity of histone deacetylases are needed for this extensive gene recruitment to the nuclear periphery.
基因组的组织并非随机,对正确功能至关重要。具体而言,核膜在基因调控中起着关键作用。它通常构成一个抑制性环境,但包括芽殖酵母中的GAL位点在内的几个基因在激活时会被招募到核周边。在这里,我们结合成像和计算建模来探究单个基因位点与核膜的关联如何影响周围的染色体结构。对整个酵母染色体的系统分析表明,GAL位点的周边招募是大规模重排的一部分,该重排使许多染色体区域更靠近核膜。这个过程可能是由几个独立的锚定位点的存在引起的。为了确定周边锚定所需的新因子,我们进行了全基因组筛选,并证明组蛋白乙酰转移酶SAGA和组蛋白去乙酰化酶的活性是这种广泛的基因招募到核周边所必需的。