CTCF negatively regulates HOXA10 expression in breast cancer cells

作者: Muhammad Mustafa , Ji-Yeon Lee , Myoung Hee Kim

DOI: 10.1016/J.BBRC.2015.10.058

关键词:

摘要: HOX genes not only play important roles in defining body patterning during embryonic development, but also control numerous cellular events adult cells. Deregulated gene expression different cancers including breast cancer is now increasingly being reported. Given that human HOXA cluster marked with several CTCF binding sites, we investigated whether the presence of associated directly Several genes, such as HOXA4, HOXA5 and HOXA10, were deregulated by overexpression knockdown MCF-7 cells. Among these HOXA10 an emerging tumor suppressor for its role activation p53 countering tumorigenesis cancer. Here provided evidences functions a negative regulator The putative promoter region lies between 5.3 6.1 kb upstream start codon activity was negatively regulated CTCF. Together in-silico analysis in vitro mutation assay identified 20 bp motif flanking core element HOXA10. kept inactivated maintaining H3K27me3 inactivation marks Epigenetic silencing cells may contribute towards decreasing apoptosis promoting metastasis.

参考文章(25)
Jennifer E. Phillips, Victor G. Corces, CTCF: Master Weaver of the Genome Cell. ,vol. 137, pp. 1194- 1211 ,(2009) , 10.1016/J.CELL.2009.06.001
M. Xu, G.-N. Zhao, X. Lv, G. Liu, L. Y. Wang, D.-L. Hao, J. Wang, D.-P. Liu, C.-C. Liang, CTCF Controls HOXA Cluster Silencing and Mediates PRC2-Repressive Higher-Order Chromatin Structure in NT2/D1 Cells Molecular and Cellular Biology. ,vol. 34, pp. 3867- 3879 ,(2014) , 10.1128/MCB.00567-14
B.-K. Lee, A. A. Bhinge, A. Battenhouse, R. M. McDaniell, Z. Liu, L. Song, Y. Ni, E. Birney, J. D. Lieb, T. S. Furey, G. E. Crawford, V. R. Iyer, Cell-type specific and combinatorial usage of diverse transcription factors revealed by genome-wide binding studies in multiple human cells Genome Research. ,vol. 22, pp. 9- 24 ,(2012) , 10.1101/GR.127597.111
V Carrie Bromleigh, Leonard P Freedman, p21 is a transcriptional target of HOXA10 in differentiating myelomonocytic cells Genes & Development. ,vol. 14, pp. 2581- 2586 ,(2000) , 10.1101/GAD.817100
E M Klenova, R H Nicolas, H F Paterson, A F Carne, C M Heath, G H Goodwin, P E Neiman, V V Lobanenkov, CTCF, a conserved nuclear factor required for optimal transcriptional activity of the chicken c-myc gene, is an 11-Zn-finger protein differentially expressed in multiple forms. Molecular and Cellular Biology. ,vol. 13, pp. 7612- 7624 ,(1993) , 10.1128/MCB.13.12.7612
France Docquier, Dawn Farrar, Vivien D'Arcy, Igor Chernukhin, Abigail F. Robinson, Dmitry Loukinov, Sergei Vatolin, Svetlana Pack, Alan Mackay, Robert A. Harris, Heather Dorricott, Michael J. O'Hare, Victor Lobanenkov, Elena Klenova, Heightened Expression of CTCF in Breast Cancer Cells Is Associated with Resistance to Apoptosis Cancer Research. ,vol. 65, pp. 5112- 5122 ,(2005) , 10.1158/0008-5472.CAN-03-3498
Claudia Fabiola Méndez-Catalá, Svetlana Gretton, Alexander Vostrov, Elena Pugacheva, Dawn Farrar, Yoko Ito, France Docquier, Georgia-Xanthi Kita, Adele Murrell, Victor Lobanenkov, Elena Klenova, A Novel Mechanism for CTCF in the Epigenetic Regulation of Bax in Breast Cancer Cells Neoplasia. ,vol. 15, pp. 898- 912 ,(2013) , 10.1593/NEO.121948
H. Wang, M. T. Maurano, H. Qu, K. E. Varley, J. Gertz, F. Pauli, K. Lee, T. Canfield, M. Weaver, R. Sandstrom, R. E. Thurman, R. Kaul, R. M. Myers, J. A. Stamatoyannopoulos, Widespread plasticity in CTCF occupancy linked to DNA methylation Genome Research. ,vol. 22, pp. 1680- 1688 ,(2012) , 10.1101/GR.136101.111
Igor Chernukhin, Shaharum Shamsuddin, Sung Yun Kang, Rosita Bergström, Yoo-Wook Kwon, WenQiang Yu, Joanne Whitehead, Rituparna Mukhopadhyay, France Docquier, Dawn Farrar, Ian Morrison, Marc Vigneron, Shwu-Yuan Wu, Cheng-Ming Chiang, Dmitri Loukinov, Victor Lobanenkov, Rolf Ohlsson, Elena Klenova, CTCF interacts with and recruits the largest subunit of RNA polymerase II to CTCF target sites genome-wide. Molecular and Cellular Biology. ,vol. 27, pp. 1631- 1648 ,(2007) , 10.1128/MCB.01993-06
Yoko Takahashi, Jun-ichi Hamada, Katsuhiko Murakawa, Minoru Takada, Mitsuhiro Tada, Ikuko Nogami, Nobuyasu Hayashi, Shoji Nakamori, Morito Monden, Masaki Miyamoto, Hiroyuki Katoh, Tetsuya Moriuchi, Expression profiles of 39 HOX genes in normal human adult organs and anaplastic thyroid cancer cell lines by quantitative real-time RT-PCR system. Experimental Cell Research. ,vol. 293, pp. 144- 153 ,(2004) , 10.1016/J.YEXCR.2003.09.024