Preferential associations between co-regulated genes reveal a transcriptional interactome in erythroid cells.
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.
Schoenfelder
Stefan
S
Laboratory of Chromatin and Gene Expression, Babraham Research Campus, Cambridge, UK.
Sexton
Tom
T
Chakalova
Lyubomira
L
Cope
Nathan F
NF
Horton
Alice
A
Andrews
Simon
S
Kurukuti
Sreenivasulu
S
Mitchell
Jennifer A
JA
Umlauf
David
D
Dimitrova
Daniela S
DS
Eskiw
Christopher H
CH
Luo
Yanquan
Y
Wei
Chia-Lin
CL
Ruan
Yijun
Y
Bieker
James J
JJ
Fraser
Peter
P
D000818:Animals; D047369:Chromatin Immunoprecipitation; D041905:Erythroid Cells / Q000166:cytology / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods*; D005914:Globins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011485:Protein Binding
D051741:Kruppel-Like Transcription Factors; C080774:erythroid Kruppel-like factor; D005914:Globins