Tissue specific CTCF occupancy and boundary function at the human growth hormone locus.
Tissue specific CTCF occupancy and boundary function at the human growth hormone locus.
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DOI：
10.1093/nar/gku139
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发表时间：
2014-04
影响因子：
14.9
通讯作者：
Liebhaber SA
中科院分区：
文献类型：
--
作者：
Tsai YC;Cooke NE;Liebhaber SA
The robust and tissue-specific activation of the human growth hormone (hGH) gene cluster in the pituitary and placenta constitutes an informative model for analysis of gene regulation. The five-gene hGH cluster is regulated by two partially overlapping sets of DNase I hypersensitive sites (HSs) that constitute the pituitary (HSI, II, III and V) and placental (HSIII, IV, and V) locus control regions (LCRs). The single placenta-specific LCR component, HSIV, is located at −30 kb to the cluster. Here we generate a series of hGH/BAC transgenes specifically modified to identify structural features of the hGH locus required for its appropriate placental expression. We find that placental specificity is dependent on the overall multigene configuration of the cluster whereas the distance between the cluster and its LCR impacts the level of placental expression. We further observe that a major function of the placental hGH LCR is to insulate the transgene locus from site-of-integration effects. This insulation activity is linked to placenta-specific occupancy of the chromatin architectural protein, CTCF, at HSIV. These data reveal a remarkable combination of structural configurations and regulatory determinants that must work in concert to insure robust and tightly controlled expression from a complex multigene locus.
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影响因子：
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作者：
ENCODE Project Consortium
通讯作者：
ENCODE Project Consortium
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作者：
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通讯作者：
GELINAS, RE
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