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PLoS One. 2012;7(3):e31484. doi: 10.1371/journal.pone.0031484. Epub 2012 Mar 1.

Mapping and functional characterisation of a CTCF-dependent insulator element at the 3' border of the murine Scl transcriptional domain.

Author information

  • 1Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom. gf246@cam.ac.uk

Abstract

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

PMID:
22396734
[PubMed - indexed for MEDLINE]
PMCID:
PMC3291548
Free PMC Article

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