Mapping and Functional Characterisation of a CTCF-Dependent Insulator Element at the 3′ Border of the Murine Scl Transcriptional Domain

作者: George A Follows , Rita Ferreira , Mary E Janes , Dominik Spensberger , Francesco Cambuli

DOI: 10.1371/JOURNAL.PONE.0031484

关键词:

摘要: The Scl gene encodes a transcription factor essential for haematopoietic development. is regulated by panel of cis-elements spread over 55 kb with the most distal 3′ element being located downstream neighbouring Map17, which co-regulated in cells. Scl/Map17 domain flanked upstream ubiquitously expressed Sil and cluster Cyp genes active liver, but mechanisms responsible delineating boundaries remain unclear. Here we report identification DNaseI hypersensitive site at end 45 start site. This boundary inactive chromatin, does not function as classical tissue-specific enhancer, binds CTCF both necessary sufficient insulator cells vitro. Moreover, transgenic reporter assay, expression promoter brain was increased incorporation 350 bp flanking fragments from +45 element. Our data suggests that region functions separates transcriptional domains, raise possibility this may be useful improving constructs.

参考文章(39)
G.P. Pfeifer, H.H. Chen, J. Komura, Arthur D. Riggs, Chromatin structure analysis by ligation-mediated and terminal transferase-mediated polymerase chain reaction. Methods in Enzymology. ,vol. 304, pp. 548- 571 ,(1999) , 10.1016/S0076-6879(99)04032-X
L. Robb, N. J. Elwood, A. G. Elefanty, F. Köntgen, R. Li, L. D. Barnett, C. G. Begley, The scl gene product is required for the generation of all hematopoietic lineages in the adult mouse. The EMBO Journal. ,vol. 15, pp. 4123- 4129 ,(1996) , 10.1002/J.1460-2075.1996.TB00787.X
Cara K. Bradley, Elena A. Takano, Mark A. Hall, Joachim R. Göthert, Alan R. Harvey, C. Glenn Begley, J. Anke M. van Eekelen, The essential haematopoietic transcription factor Scl is also critical for neuronal development European Journal of Neuroscience. ,vol. 23, pp. 1677- 1689 ,(2006) , 10.1111/J.1460-9568.2006.04712.X
Amy T. Hark, Christopher J. Schoenherr, David J. Katz, Robert S. Ingram, John M. Levorse, Shirley M. Tilghman, CTCF mediates methylation-sensitive enhancer-blocking activity at the H19/Igf2 locus Nature. ,vol. 405, pp. 486- 489 ,(2000) , 10.1038/35013106
Adam C. Bell, Gary Felsenfeld, Methylation of a CTCF-dependent boundary controls imprinted expression of the Igf2 gene Nature. ,vol. 405, pp. 482- 485 ,(2000) , 10.1038/35013100
B. Gottgens, A. R. Green, M. Stanley, C. G. Begley, M.-J. Sanchez, S. Hunter, A. M. Sinclair, An SCL 3' enhancer targets developing endothelium together with embryonic and adult haematopoietic progenitors. Development. ,vol. 126, pp. 3891- 3904 ,(1999) , 10.1242/DEV.126.17.3891
C. Glenn Begley, Anthony R. Green, The SCL gene: from case report to critical hematopoietic regulator. Blood. ,vol. 93, pp. 2760- 2770 ,(1999) , 10.1182/BLOOD.V93.9.2760
Lev Silberstein, María‐José Sánchez, Merav Socolovsky, Ying Liu, Gary Hoffman, Sarah Kinston, Sandie Piltz, Mark Bowen, Laure Gambardella, Anthony R Green, Berthold Göttgens, None, Transgenic analysis of the stem cell leukemia +19 stem cell enhancer in adult and embryonic hematopoietic and endothelial cells. Stem Cells. ,vol. 23, pp. 1378- 1388 ,(2005) , 10.1634/STEMCELLS.2005-0090
J. E. Pimanda, K. Ottersbach, K. Knezevic, S. Kinston, W. Y. I. Chan, N. K. Wilson, J.-R. Landry, A. D. Wood, A. Kolb-Kokocinski, A. R. Green, D. Tannahill, G. Lacaud, V. Kouskoff, B. Gottgens, Gata2, Fli1, and Scl form a recursively wired gene-regulatory circuit during early hematopoietic development Proceedings of the National Academy of Sciences of the United States of America. ,vol. 104, pp. 17692- 17697 ,(2007) , 10.1073/PNAS.0707045104
Miklos Gaszner, Gary Felsenfeld, Insulators: exploiting transcriptional and epigenetic mechanisms Nature Reviews Genetics. ,vol. 7, pp. 703- 713 ,(2006) , 10.1038/NRG1925