Investigation of genes co-regulated by Notch-1 intra-cellular domain and CBF-1 at transcription level in the whole genome of human pancreatic cancer BxPC3 cells

doi:10.3969/j.issn.1006-7795.2014.02.019

Abstract

Abstract:

Objective Looking for the potential genes co-regulated by Notch-1 intra-cellular domain(NICD) and CBF-1 at transcription level in the whole genome of human pancreatic cancer cell BxPC3 cells; investigating characteristics of those genes such as distribution, functions and classification; suggesting the potential functions and regulatory pattern of Notch signalling pathway based on the data obtained. Methods Chromatin immuno-precipitation(ChIP) coupled with Illumina/Solexa-platform based high-throughput sequencing was employed to illustrate the profile of synergistic transcription between NICD and CBF-1 at genome-wide level in human pancreatic cancer BxPC3 cells. Results 1) The numbers of qualified reads for NICD and CBF-1 samples are 14 287 722 and 14 289 280, 11 782 027 and 11 711 920 of which are uniquely matched with human reference genome, respectively. 2) The numbers of peaks for NICD and CBF-1 samples are 385 and 492; the peak region covers 318 344 bp and 383 768 bp, each of which accounts for 0.01% of whole genome. 3) Regardless of NICD or CBF-1 samples, most peaks scatter at intergenic and intronic region and only less than 5% of them locate in exonic region. 4) 150 out of 385 peaks for NICD samples and 287 out of 492 peaks for CBF-1 samples can be uniquely matched with a human gene, 93 of which are the same between two groups. 5) The details of those genes, such as names, locations and functions, were indicated by gene ontology(GO) analysis and gene database mining. Conclusion More unknown genes co-regulated by NICD and CBF-1 at transcription level were discovered in human pancreatic BxPC3 cells; the distribution, functions and classification of them were demonstrated; the potential functions and regulatory pattern of Notch signalling pathway were implied based on the data obtained.

Key words: Notch signalling pathway, CBF-1, chromatin immuno-precipitation, high-throughput sequencing, peaks, gene ontology analysis

CLC Number:

R329.2

Wang Lange, Zhang Yuxiang. Investigation of genes co-regulated by Notch-1 intra-cellular domain and CBF-1 at transcription level in the whole genome of human pancreatic cancer BxPC3 cells[J]. Journal of Capital Medical University, 2014, 35(2): 237-242.

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URL: https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/10.3969/j.issn.1006-7795.2014.02.019

https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/Y2014/V35/I2/237

References

[1] Aguirre A, Rubio M E, Gallo V. Notch and EGFR pathway interaction regulates neural stem cell number and self-renewal[J]. Nature, 2010, 467(7313):323-327.

[2] Artavanis-Tsakonas S, Rand M D, et al. Notch signaling: cell fate control and signal integration in development[J]. Science, 1999, 284(5415):770-776.

[3] Lai E C. Notch signaling: control of cell communication and cell fate[J]. Development, 2004, 131(5):965-973.

[4] Liu Z J, Shirakawa T, Li Y, et al. Regulation of Notch1 and Dll4 by vascular endothelial growth factor in arterial endothelial cells: implications for modulating arteriogenesis and angiogenesis[J]. Mol Cell Biol, 2003, 23(1):14-25.

[5] Yoon K, Gaiano N. Notch signaling in the mammalian central nervous system: insights from mouse mutants[J]. Nat Neurosci, 2005, 8(6):709-715.

[6] Bolos V, Grego-Bessa J, de la Pompa J L. Notch signaling in development and cancer[J]. Endocr Rev, 2007, 28(3):339-363.

[7] Avila J L, Kissil J L. Notch signaling in pancreatic cancer: oncogene or tumor suppressor?[J]. Trends Mol Med, 2013, 19(5):320-327.

[8] Wang Z, Ahmad A, Li Y, et al. Targeting notch to eradicate pancreatic cancer stem cells for cancer therapy[J]. Anticancer Res, 2011, 31(4):1105-1113.

[9] Munro S, Freeman M, The notch signalling regulator fringe acts in the Golgi apparatus and requires the glycosyltransferase signature motif DXD[J]. Curr Biol, 2000, 10(14):813-820.

[10] Borggrefe T, Liefke R. Fine-tuning of the intracellular canonical Notch signaling pathway[J]. Cell Cycle, 2012, 11(2):264-276.

[11] LaVoie M J, Selkoe D J. The Notch ligands, Jagged and Delta, are sequentially processed by alpha-secretase and presenilin/gamma-secretase and release signaling fragments[J]. J Biol Chem, 2003, 278(36):34427-34437.

[12] Brou C, Logeat F, Gupta N, et al. A novel proteolytic cleavage involved in Notch signaling: the role of the disintegrin-metalloprotease TACE[J]. Mol Cell, 2000, 5(2):207-216.

[13] Bray S J. Notch signalling: a simple pathway becomes complex[J]. Nat Rev Mol Cell Biol, 2006, 7(9):678-689.

[14] Mumm J S, Kopan R. Notch signaling: from the outside in[J]. Dev Biol, 2000, 228(2):151-165.

[15] Lai E C. Keeping a good pathway down: transcriptional repression of Notch pathway target genes by CSL proteins[J]. EMBO Rep, 2002, 3(9):840-845.

[16] Metzker M L. Sequencing technologies-the next generation[J]. Nat Rev Genet, 2010, 11(1):31-46.

[17] Skrtic M, Sriskanthadevan S, Jhas B, et al. Inhibition of mitochondrial translation as a therapeutic strategy for human acute myeloid leukemia[J]. Cancer Cell, 2011, 20(5):674-688.

[18] Gebre-Medhin M, Kindblom L G, Wennbo H, et al. Growth hormone receptor is expressed in human breast cancer[J]. Am J Pathol, 2001, 158(4):1217-1222.

[19] Kidokoro T, Tanikawa C, Furukawa Y, et al. CDC20, a potential cancer therapeutic target, is negatively regulated by p53[J]. Oncogene, 2008, 27(11):1562-1571.

[20] Normanno N, De Luca A, Bianco C, et al. Epidermal growth factor receptor(EGFR) signaling in cancer[J]. Gene, 2006, 366(1):2-16.

[21] Wang Z, Li Y, Kong D, et al. Cross-talk between miRNA and Notch signaling pathways in tumor development and progression[J]. Cancer Lett, 2010, 292(2):141-148.

[22] Agrawal S, Archer C, Schaffer D V. Computational models of the Notch network elucidate mechanisms of context-dependent signaling[J]. PLoS Comput Biol, 2009, 5(5):e1000390.

[23] Shimojo H, Ohtsuka T, Kageyama R. Oscillations in notch signaling regulate maintenance of neural progenitors[J]. Neuron, 2008, 58(1):52-64.

[24] Shibata M, Nakao H, Kiyonari H, et al. MicroRNA-9 regulates neurogenesis in mouse telencephalon by targeting multiple transcription factors[J]. J Neurosci, 2011, 31(9):3407-3422.

[25] Bonev B, Stanley P, Papalopulu N. MicroRNA-9 Modulates Hes1 ultradian oscillations by forming a double-negative feedback loop[J]. Cell Rep, 2012, 2(1):10-18.