CTCF-binding sites within the H19 ICR differentially regulate local chromatin structures and cis-acting functions |
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| Authors: | Samuel Keating Assam El-Osta |
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| Affiliation: | 1.Epigenetics in Human Health and Disease Laboratory; Baker IDI Heart and Diabetes Institute; The Alfred Medical Research and Education Precinct; Melbourne, VIC Australia;2.Epigenomics Profiling Facility; Baker IDI Heart and Diabetes Institute; The Alfred Medical Research and Education Precinct; Melbourne, VIC Australia;3.Department of Pathology; The University of Melbourne; Melbourne, VIC Australia;4.Faculty of Medicine; Monash University; Melbourne, VIC Australia |
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| Abstract: | It is generally assumed that CTCF-binding sites are synonymous with the demarcation of expression domains by promoting the formation of chromatin loops. We have proposed earlier, however, that such features may be context-dependent. In support of this notion, we show here that chromatin loop structures, impinging on CTCF-binding sites 1/2 and 3/4 at the 5′ and 3′-ends, respectively, within the maternal allele of the H19 imprinting control region (ICR), differ significantly. Although abrogation of CTCF binding to the maternal H19 ICR allele results in loss of chromatin loops in the 3′-region, there is a dramatic gain of long-range chromatin loops impinging on the 5′-region. As the degree of occupancy of its four CTCF-binding sites discriminates between the chromatin insulator and replication timing functions, we submit that the CTCF-binding sites within the H19 ICR are functionally diverse and organize context-dependent higher order chromatin conformations. |
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| Keywords: | Chromatin CTCF insulator imprinting replication timing |
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