Nucleoporin-mediated regulation of cell identity genes.
The organization of the genome in the three-dimensional space of the nucleus is coupled with cell type-specific gene expression. However, how nuclear architecture influences transcription that governs cell identity remains unknown. Here, we show that nuclear pore complex (NPC) components Nup93 and Nup153 bind superenhancers (SE), regulatory structures that drive the expression of key genes that specify cell identity. We found that nucleoporin-associated SEs localize preferentially to the nuclear periphery, and absence of Nup153 and Nup93 results in dramatic transcriptional changes of SE-associated genes. Our results reveal a crucial role of NPC components in the regulation of cell type-specifying genes and highlight nuclear architecture as a regulatory layer of genome functions in cell fate.
Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037, USA.
Arkaitz
A
Ibarra
Integrative Genomics and Bioinformatics Core, Salk Institute for Biological Studies, La Jolla, California 92037, USA.
Chris
C
Benner
Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037, USA.
Swati
S
Tyagi
Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037, USA.
Jonah
J
Cool
Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037, USA.
Martin W
MW
Hetzer
D002454:Cell Differentiation / Q000235:genetics*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism; D004742:Enhancer Elements, Genetic / Q000502:physiology; D005786:Gene Expression Regulation / Q000235:genetics*; D016678:Genome / Q000235:genetics; D006801:Humans; D009685:Nuclear Envelope / Q000378:metabolism; D028861:Nuclear Pore Complex Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport
D002843:Chromatin; C079377:NUP153 protein, human; D028861:Nuclear Pore Complex Proteins
cell identity; nuclear architecture; nuclear pore complex; nucleoporin; superenhancer; transcription