Open AccessTranscription-dependent radial distribution of TCF7L2 regulated genes in chromosome territories
Author(s) -
Keyvan Torabi,
Darawalee Wangsa,
Immaculada Ponsa,
Markus Brown,
Anna Bosch,
María Vila-Casadesús,
Tatiana S. Karpova,
María Isabel Calvo,
Antoni Castells,
Rosa Miró,
Thomas Ried,
Jordi Camps
Publication year - 2017
Publication title -
chromosoma
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.945
H-Index - 86
eISSN - 1432-0886
pISSN - 0009-5915
DOI - 10.1007/s00412-017-0629-6
Subject(s) - biology , gene , tcf4 , wnt signaling pathway , genetics , chromosome , gene expression , gene silencing , microbiology and biotechnology , fluorescence in situ hybridization , promoter
Human chromosomes occupy distinct territories in the interphase nucleus. Such chromosome territories (CTs) are positioned according to gene density. Gene-rich CTs are generally located in the center of the nucleus, while gene-poor CTs are positioned more towards the nuclear periphery. However, the association between gene expression levels and the radial positioning of genes within the CT is still under debate. In the present study, we performed three-dimensional fluorescence in situ hybridization experiments in the colorectal cancer cell lines DLD-1 and LoVo using whole chromosome painting probes for chromosomes 8 and 11 and BAC clones targeting four genes with different expression levels assessed by gene expression arrays and RT-PCR. Our results confirmed that the two over-expressed genes, MYC on chromosome 8 and CCND1 on chromosome 11, are located significantly further away from the center of the CT compared to under-expressed genes on the same chromosomes, i.e., DLC1 and SCN3B. When CCND1 expression was reduced after silencing the major transcription factor of the WNT/β-catenin signaling pathway, TCF7L2, the gene was repositioned and mostly detected in the interior of the CT. Thus, we suggest a non-random distribution in which over-expressed genes are located more towards the periphery of the respective CTs.