Nuclear Aggregation of Olfactory Receptor Genes Governs Their Monogenic Expression

被引：244

作者：

Clowney, E. Josephine ^{[1
]}

LeGros, Mark A. ^{[2
,4
]}

Mosley, Colleen P. ^{[2
]}

Clowney, Fiona G. ^{[2
]}

Markenskoff-Papadimitriou, Eirene C. ^{[3
]}

Myllys, Markko ^{[5
]}

Barnea, Gilad ^{[6
]}

Larabell, Carolyn A. ^{[2
,4
]}

Lomvardas, Stavros ^{[1
,2
,3
]}

机构：

[1] Univ Calif San Francisco, Program Biomed Sci, San Francisco, CA 94158 USA

[2] Univ Calif San Francisco, Dept Anat, San Francisco, CA 94158 USA

[3] Univ Calif San Francisco, Program Neurosci, San Francisco, CA 94158 USA

[4] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Phys Biosci Div, Berkeley, CA 94720 USA

[5] Univ Jyvaskyla, Dept Phys, FI-40014 Jyvaskyla, Finland

[6] Brown Univ, Dept Neurosci, Providence, RI 02912 USA

来源：

CELL | 2012年 / 151卷 / 04期

基金：

美国国家卫生研究院; 美国国家科学基金会;

关键词：

ORGANIZATION; CHROMATIN; CHOICE; MORPHOLOGY; PROMOTER; LAMINA; GENOME; MICE;

D O I：

10.1016/j.cell.2012.09.043

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Gene positioning and regulation of nuclear architecture are thought to influence gene expression. Here, we show that, in mouse olfactory neurons, silent olfactory receptor (OR) genes from different chromosomes converge in a small number of heterochromatic foci. These foci are OR exclusive and form in a cell-type-specific and differentiation-dependent manner. The aggregation of OR genes is developmentally synchronous with the downregulation of lamin b receptor (LBR) and can be reversed by ectopic expression of LBR in mature olfactory neurons. LBR-induced reorganization of nuclear architecture and disruption of OR aggregates perturbs the singularity of OR transcription and disrupts the targeting specificity of the olfactory neurons. Our observations propose spatial sequestering of heterochromatinized OR family members as a basis of monogenic and monoallelic gene expression.

引用

页码：724 / 737

页数：14

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