Long-range enhancers on 8q24 regulate c-Myc

被引：183

作者：

Sotelo, Jose ^{[1
,2
]}

Esposito, Dominic ^{[1
,3
]}

Duhagon, Maria Ana ^{[4
]}

Banfield, Kelley ^{[1
,2
]}

Mehalko, Jennifer ^{[1
,3
]}

Liao, Hongling ^{[1
,2
]}

Stephens, Robert M. ^{[1
,5
]}

Harris, Timothy J. R. ^{[1
]}

Munroe, David J. ^{[1
]}

Wu, Xiaolin ^{[1
,2
]}

机构：

[1] NCI, Adv Technol Program, Frederick, MD 21702 USA

[2] NCI, Lab Mol Technol, Frederick, MD 21702 USA

[3] NCI, Prot Express Lab, Frederick, MD 21702 USA

[4] NCI, Canc Stem Cell Sect, Lab Canc Prevent, Frederick, MD 21702 USA

[5] SAIC Frederick Inc, Adv Biomed Comp Ctr, NCI, Frederick, MD 21702 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2010年 / 107卷 / 07期

基金：

美国国家卫生研究院;

关键词：

COMPARATIVE GENOMIC HYBRIDIZATION; WIDE ASSOCIATION SCAN; PROSTATE-CANCER; COLORECTAL-CANCER; CHROMOSOME CONFORMATION; RISK LOCUS; IN-VIVO; EXPRESSION; PROMOTER; GENE;

D O I：

10.1073/pnas.0906067107

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Recent genomewide association studies have found multiple genetic variants on chromosome 8q24 that are significantly associated with an increased susceptibility to prostate, colorectal, and breast cancer. These risk loci are located in a "gene desert," a few hundred kilobases telomeric to the Myc gene. To date, the biological mechanism(s) underlying these associations remain unclear. It has been speculated that these 8q24 genetic variant(s) might affect Myc expression by altering its regulation or amplification status. Here, we show that multiple enhancer elements are present within this region and that they can regulate transcription of Myc. We also demonstrate that one such enhancer element physically interacts with the Myc promoter via transcription factor Tcf-4 binding and acts in an allele specific manner to regulate Myc expression.

引用

页码：3001 / 3005

页数：5

共 34 条

[1] A common variant associated with prostate cancer in European and African populations [J].

Amundadottir, Laufey T. ;

Sulem, Patrick ;

Gudmundsson, Julius ;

Helgason, Agnar ;

Baker, Adam ;

Agnarsson, Bjarni A. ;

Sigurdsson, Asgeir ;

Benediktsdottir, Kristrun R. ;

Cazier, Jean-Baptiste ;

Sainz, Jesus ;

Jakobsdottir, Margret ;

Kostic, Jelena ;

Magnusdottir, Droplaug N. ;

Ghosh, Shyamali ;

Agnarsson, Kari ;

Birgisdottir, Birgitta ;

Le Roux, Louise ;

Olafsdottir, Adalheidur ;

Blondal, Thorarinn ;

Andresdottir, Margret ;

Gretarsdottir, Olafia Svandis ;

Bergthorsson, Jon T. ;

Gudbjartsson, Daniel ;

Gylfason, Arnaldur ;

Thorleifsson, Gudmar ;

Manolescu, Andrei ;

Kristjansson, Kristleifur ;

Geirsson, Gudmundur ;

Isaksson, Helgi ;

Douglas, Julie ;

Johansson, Jan-Erik ;

Balter, Katarina ;

Wiklund, Fredrik ;

Montie, James E. ;

Yu, Xiaoying ;

Suarez, Brian K. ;

Ober, Carole ;

Cooney, Kathleen A. ;

Gronberg, Henrik ;

Catalona, William J. ;

Einarsson, Gudmundur V. ;

Barkardottir, Rosa B. ;

Gulcher, Jeffrey R. ;

Kong, Augustine ;

Thorsteinsdottir, Unnur ;

Stefansson, Kari .

NATURE GENETICS, 2006, 38 (06) :652-658

[2]

Cher ML, 1996, CANCER RES, V56, P3091

[3] Capturing chromosome conformation [J].

Dekker, J ;

Rippe, K ;

Dekker, M ;

Kleckner, N .

SCIENCE, 2002, 295 (5558) :1306-1311

[4] Array comparative genomic hybridization analysis of colorectal cancer cell lines and primary carcinomas [J].

Douglas, EJ ;

Fiegler, H ;

Rowan, A ;

Halford, S ;

Bicknell, DC ;

Bodmer, W ;

Tomlinson, IPM ;

Carter, NP .

CANCER RESEARCH, 2004, 64 (14) :4817-4825

[5] Genome-wide association study identifies novel breast cancer susceptibility loci [J].

Easton, Douglas F. ;

Pooley, Karen A. ;

Dunning, Alison M. ;

Pharoah, Paul D. P. ;

Thompson, Deborah ;

Ballinger, Dennis G. ;

Struewing, Jeffery P. ;

Morrison, Jonathan ;

Field, Helen ;

Luben, Robert ;

Wareham, Nicholas ;

Ahmed, Shahana ;

Healey, Catherine S. ;

Bowman, Richard ;

Meyer, Kerstin B. ;

Haiman, Christopher A. ;

Kolonel, Laurence K. ;

Henderson, Brian E. ;

Le Marchand, Loic ;

Brennan, Paul ;

Sangrajrang, Suleeporn ;

Gaborieau, Valerie ;

Odefrey, Fabrice ;

Shen, Chen-Yang ;

Wu, Pei-Ei ;

Wang, Hui-Chun ;

Eccles, Diana ;

Evans, D. Gareth ;

Peto, Julian ;

Fletcher, Olivia ;

Johnson, Nichola ;

Seal, Sheila ;

Stratton, Michael R. ;

Rahman, Nazneen ;

Chenevix-Trench, Georgia ;

Bojesen, Stig E. ;

Nordestgaard, Borge G. ;

Axelsson, Christen K. ;

Garcia-Closas, Montserrat ;

Brinton, Louise ;

Chanock, Stephen ;

Lissowska, Jolanta ;

Peplonska, Beata ;

Nevanlinna, Heli ;

Fagerholm, Rainer ;

Eerola, Hannaleena ;

Kang, Daehee ;

Yoo, Keun-Young ;

Noh, Dong-Young ;

Ahn, Sei-Hyun .

NATURE, 2007, 447 (7148) :1087-U7

[6] Admixture mapping identifies 8q24 as a prostate cancer risk locus in African-American men [J].

Freedman, Matthew L. ;

Haiman, Christopher A. ;

Patterson, Nick ;

McDonald, Gavin J. ;

Tandon, Arti ;

Waliszewska, Alicja ;

Penney, Kathryn ;

Steen, Robert G. ;

Ardlie, Kristin ;

John, Esther M. ;

Clakley-Girvan, Ingrid ;

Whitternore, Alice S. ;

Cooney, Kathleen A. ;

Ingles, Sue A. ;

Altshuler, David ;

Henderson, Brian E. ;

Reich, David .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (38) :14068-14073

[7] Characterization of an enhancer element in the proximal promoter of the mouse glucagon receptor gene [J].

Geiger, A ;

Salazar, G ;

Le Cam, A ;

Kervran, A .

BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION, 2001, 1517 (02) :236-242

[8] Genome-wide association study identifies a second prostate cancer susceptibility variant at 8q24 [J].

Gudmundsson, Julius ;

Sulem, Patrick ;

Manolescu, Andrei ;

Amundadottir, Laufey T. ;

Gudbjartsson, Daniel ;

Helgason, Agnar ;

Rafnar, Thorunn ;

Bergthorsson, Jon T. ;

Agnarsson, Bjarni A. ;

Baker, Adam ;

Sigurdsson, Asgeir ;

Benediktsdottir, Kristrun R. ;

Jakobsdottir, Margret ;

Xu, Jianfeng ;

Blondal, Thorarinn ;

Kostic, Jelena ;

Sun, Jielin ;

Ghosh, Shyamali ;

Stacey, Simon N. ;

Mouy, Magali ;

Saemundsdottir, Jona ;

Backman, Valgerdur M. ;

Kristjansson, Kristleifur ;

Tres, Alejandro ;

Partin, Alan W. ;

Albers-Akkers, Marjo T. ;

Marcos, Javier Godino-Ivan ;

Walsh, Patrick C. ;

Swinkels, Dorine W. ;

Navarrete, Sebastian ;

Isaacs, Sarah D. ;

Aben, Katja K. ;

Graif, Theresa ;

Cashy, John ;

Ruiz-Echarri, Manuel ;

Wiley, Kathleen E. ;

Suarez, Brian K. ;

Witjes, J. Alfred ;

Frigge, Mike ;

Ober, Carole ;

Jonsson, Eirikur ;

Einarsson, Gudmundur V. ;

Mayordomo, Jose I. ;

Kiemeney, Lambertus A. ;

Isaacs, William B. ;

Catalona, William J. ;

Barkardottir, Rosa B. ;

Gulcher, Jeffrey R. ;

Thorsteinsdottir, Unnur ;

Kong, Augustine .

NATURE GENETICS, 2007, 39 (05) :631-637

[9] Quantitative analysis of chromosome conformation capture assays (3C-qPCR) [J].

Hagege, Helene ;

Klous, Petra ;

Braem, Caroline ;

Splinter, Erik ;

Dekker, Job ;

Cathala, Guy ;

de Laat, Wouter ;

Forne, Thierry .

NATURE PROTOCOLS, 2007, 2 (07) :1722-1733

[10] A common genetic risk factor for colorectal and prostate cancer [J].

Haiman, Christopher A. ;

Le Marchand, Loic ;

Yamamato, Jennifer ;

Stram, Daniel O. ;

Sheng, Xin ;

Kolonel, Laurence N. ;

Wu, Anna H. ;

Reich, David ;

Henderson, Brian E. .

NATURE GENETICS, 2007, 39 (08) :954-956

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