Preferential associations between co-regulated genes reveal a transcriptional interactome in erythroid cells

被引:512
作者
Schoenfelder, Stefan [1 ]
Sexton, Tom [1 ]
Chakalova, Lyubomira [1 ]
Cope, Nathan F. [1 ]
Horton, Alice [1 ]
Andrews, Simon [2 ]
Kurukuti, Sreenivasulu [1 ]
Mitchell, Jennifer A. [1 ]
Umlauf, David [1 ]
Dimitrova, Daniela S. [1 ]
Eskiw, Christopher H. [1 ]
Luo, Yanquan [3 ]
Wei, Chia-Lin [3 ]
Ruan, Yijun [3 ]
Bieker, James J. [4 ]
Fraser, Peter [1 ]
机构
[1] Lab Chromatin & Gene Express, Cambridge, England
[2] Babraham Inst, Bioinformat Grp, Cambridge, England
[3] Genome Inst Singapore, Singapore, Singapore
[4] Mt Sinai Hosp, Mt Sinai Sch Med, Dept Dev & Regenerat Biol, New York, NY 10029 USA
基金
英国医学研究理事会; 英国生物技术与生命科学研究理事会;
关键词
BETA-GLOBIN LOCUS; RNA-POLYMERASE-II; CONTROL REGION; INTERCHROMOSOMAL ASSOCIATIONS; NUCLEAR-ORGANIZATION; SPATIAL-ORGANIZATION; EKLF; EXPRESSION; SITES; FACTORIES;
D O I
10.1038/ng.496
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
The discovery of interchromosomal interactions in higher eukaryotes points to a functional interplay between genome architecture and gene expression, challenging the view of transcription as a one-dimensional process. However, the extent of interchromosomal interactions and the underlying mechanisms are unknown. Here we present the first genome-wide analysis of transcriptional interactions using the mouse globin genes in erythroid tissues. Our results show that the active globin genes associate with hundreds of other transcribed genes, revealing extensive and preferential intra- and interchromosomal transcription interactomes. We show that the transcription factor Klf1 mediates preferential co-associations of Klf1-regulated genes at a limited number of specialized transcription factories. Our results establish a new gene expression paradigm, implying that active co-regulated genes and their regulatory factors cooperate to create specialized nuclear hot spots optimized for efficient and coordinated transcriptional control.
引用
收藏
页码:53 / U71
页数:10
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