期刊
JOURNAL OF CELL SCIENCE
卷 128, 期 16, 页码 3106-3116出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.170985
关键词
Paxillin; Cohesin; Imprinting; IGF2; H19; Enhancer
类别
资金
- Human Frontier Science Program [RGP0017/2013]
- Grant Agency of Charles University [407011]
- Ministry of Education, Youth and Sports of the Czech Republic [CZ.1.07/2.3.00/30.0003, CZ.1.05/1.1.00/02.0109, CZ.1.07/2.3.00/30.0050]
- Institutional Research Concept of the Institute of Microbiology [RVO61388971]
- Institutional Research Concept of the Institute of Molecular biology [RVO: 68378050]
- Charles University [204025/2012]
- European Union [Operational Program Prague] [CZ.2.16/3.1.00/24023]
- project 'BIOCEV - Biotechnology and Biomedicine Centre of the Academy of Sciences and Charles University' - European Regional Development Fund [CZ.1.05/1.1.00/02.0109]
Paxillin (PXN) is a focal adhesion protein that has been implicated in signal transduction from the extracellular matrix. Recently, it has been shown to shuttle between the cytoplasm and the nucleus. When inside the nucleus, paxillin promotes cell proliferation. Here, we introduce paxillin as a transcriptional regulator of IGF2 and H19 genes. It does not affect the allelic expression of the two genes; rather, it regulates long-range chromosomal interactions between the IGF2 or H19 promoter and a shared distal enhancer on an active allele. Specifically, paxillin stimulates the interaction between the enhancer and the IGF2 promoter, thus activating IGF2 gene transcription, whereas it restrains the interaction between the enhancer and the H19 promoter, downregulating the H19 gene. We found that paxillin interacts with cohesin and the mediator complex, which have been shown to mediate long-range chromosomal looping. We propose that these interactions occur at the IGF2 and H19 gene cluster and are involved in the formation of loops between the IGF2 and H19 promoters and the enhancer, and thus the expression of the corresponding genes. These observations contribute to a mechanistic explanation of the role of paxillin in proliferation and fetal development.
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