Article ; Online: Mapping and functional characterisation of a CTCF-dependent insulator element at the 3' border of the murine Scl transcriptional domain.
2012 Volume 7, Issue 3, Page(s) e31484
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, ... ...
| 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. |
|---|---|
| MeSH term(s) | Animals ; Basic Helix-Loop-Helix Transcription Factors/genetics ; Basic Helix-Loop-Helix Transcription Factors/physiology ; Binding Sites ; CCCTC-Binding Factor ; Chromatin Immunoprecipitation ; Chromosome Mapping/methods ; Deoxyribonuclease I/metabolism ; Enhancer Elements, Genetic ; Genes, Reporter ; Hematopoietic Stem Cells/cytology ; Humans ; Liver/metabolism ; Mice ; Multigene Family ; Oligonucleotide Array Sequence Analysis ; Protein Structure, Tertiary ; Proto-Oncogene Proteins/genetics ; Proto-Oncogene Proteins/physiology ; Repressor Proteins/genetics ; T-Cell Acute Lymphocytic Leukemia Protein 1 ; Transcription, Genetic ; Transgenes |
| Chemical Substances | Basic Helix-Loop-Helix Transcription Factors ; CCCTC-Binding Factor ; CTCF protein, human ; Ctcf protein, mouse ; Proto-Oncogene Proteins ; Repressor Proteins ; T-Cell Acute Lymphocytic Leukemia Protein 1 ; Tal1 protein, mouse ; Deoxyribonuclease I (EC 3.1.21.1) |
| Language | English |
| Publishing date | 2012-03-01 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2267670-3 |
| ISSN | 1932-6203 ; 1932-6203 |
| ISSN (online) | 1932-6203 |
| ISSN | 1932-6203 |
| DOI | 10.1371/journal.pone.0031484 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
More links
Kategorien
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.