Transcription-dependent radial distribution of TCF7L2 regulated genes in chromosome territories.
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.
Unitat de Biologia Cel·lular i Genètica Mèdica, Departament de Biologia Cel·lular, Fisiologia i Immunologia, Facultat de Medicina, Universitat Autònoma de Barcelona, 08193, Bellaterra, Catalonia, Spain.|Gastrointestinal and Pancreatic Oncology Group, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Rosselló 153, 4th floor, 08036, Barcelona, Catalonia, Spain.
Keyvan
K
Torabi
Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892-8010, USA.
Darawalee
D
Wangsa
Unitat de Biologia Cel·lular i Genètica Mèdica, Departament de Biologia Cel·lular, Fisiologia i Immunologia, Facultat de Medicina, Universitat Autònoma de Barcelona, 08193, Bellaterra, Catalonia, Spain.|Institut de Biotecnologia i Biomedicina, Universitat Autònoma de Barcelona, 08193, Bellaterra, Catalonia, Spain.
Immaculada
I
Ponsa
Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892-8010, USA.
Markus
M
Brown
Advanced Optical Microscopy Unit, Scientific and Technologic Centers, Facultat de Medicina, Universitat de Barcelona, 08036, Barcelona, Catalonia, Spain.
Anna
A
Bosch
Gastrointestinal and Pancreatic Oncology Group, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Rosselló 153, 4th floor, 08036, Barcelona, Catalonia, Spain.
Maria
M
Vila-Casadesús
CCR/LRBGE Optical Microscopy Core, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Tatiana S
TS
Karpova
Advanced Optical Microscopy Unit, Scientific and Technologic Centers, Facultat de Medicina, Universitat de Barcelona, 08036, Barcelona, Catalonia, Spain.
Maria
M
Calvo
Gastrointestinal and Pancreatic Oncology Group, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Rosselló 153, 4th floor, 08036, Barcelona, Catalonia, Spain.
Antoni
A
Castells
Unitat de Biologia Cel·lular i Genètica Mèdica, Departament de Biologia Cel·lular, Fisiologia i Immunologia, Facultat de Medicina, Universitat Autònoma de Barcelona, 08193, Bellaterra, Catalonia, Spain.|CCR/LRBGE Optical Microscopy Core, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Rosa
R
Miró
Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892-8010, USA. riedt@mail.nih.gov.
Thomas
T
Ried
Unitat de Biologia Cel·lular i Genètica Mèdica, Departament de Biologia Cel·lular, Fisiologia i Immunologia, Facultat de Medicina, Universitat Autònoma de Barcelona, 08193, Bellaterra, Catalonia, Spain. jcamps@clinic.cat.|Gastrointestinal and Pancreatic Oncology Group, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Rosselló 153, 4th floor, 08036, Barcelona, Catalonia, Spain. jcamps@clinic.cat.
Jordi
J
Camps
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D002877:Chromosomes, Human / Q000235:genetics / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007399:Interphase; D015398:Signal Transduction; D058118:Transcription Factor 7-Like 2 Protein / Q000378:metabolism*
C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein
3D-FISH; Chromosome territory; Colorectal cancer; Gene expression; Nuclear architecture; Radial positioning