Igf2/H19 Imprinting Control Region (ICR): An Insulator or a Position-Dependent Silencer?
The imprinting control region (ICR) located far upstream of the H19 gene, in conjunction with enhancers, modulates the transcription of Igf2 and H19 genes in an allele-specific manner. On paternal inheritance, the methylated ICR silences the H19 gene and indirectly facilitates transcription from the...
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| Format: | Article |
| Language: | English |
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Wiley
2001-01-01
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| Series: | The Scientific World Journal |
| Online Access: | http://dx.doi.org/10.1100/tsw.2001.50 |
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| _version_ | 1832564070846300160 |
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| author | Subhasis Banerjee Alan Smallwood Scott Lamond Stuart Campbell Geeta Nargund |
| author_facet | Subhasis Banerjee Alan Smallwood Scott Lamond Stuart Campbell Geeta Nargund |
| author_sort | Subhasis Banerjee |
| collection | DOAJ |
| description | The imprinting control region (ICR) located far upstream of the H19 gene, in conjunction with enhancers, modulates the transcription of Igf2 and H19 genes in an allele-specific manner. On paternal inheritance, the methylated ICR silences the H19 gene and indirectly facilitates transcription from the distant Igf2 promoter, whereas on the maternal chromosome the unmethylated ICR, together with enhancers, activates transcription of the H19 gene and thereby contributes to the repression of Igf2. This repression of maternal Igf2 has recently been postulated to be due to a chromatin boundary or insulator function of the unmethylated ICR. Central to the insulator model is the site-specific binding of a ubiquitous nuclear factor CTCF which exhibits remarkable flexibility in functioning as transcriptional activator or silencer. We suggest that the ICR positioned close to the enhancers in an episomal context might function as a transcriptional silencer by virtue of interaction of CTCF with its modifiers such as SIN3A and histone deacetylases. Furthermore, a localised folded chromatin structure resulting from juxtaposition of two disparate regulatory sequences (enhancer ICR) could be the mechanistic basis of ICR-mediated position-dependent (ICR-promoter) transcriptional repression in transgenic Drosophila. |
| format | Article |
| id | doaj-art-99597ccdc8a44ead91c84bf1b4d438c2 |
| institution | Kabale University |
| issn | 1537-744X |
| language | English |
| publishDate | 2001-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | The Scientific World Journal |
| spelling | doaj-art-99597ccdc8a44ead91c84bf1b4d438c22025-02-03T01:11:49ZengWileyThe Scientific World Journal1537-744X2001-01-01121822410.1100/tsw.2001.50Igf2/H19 Imprinting Control Region (ICR): An Insulator or a Position-Dependent Silencer?Subhasis Banerjee0Alan Smallwood1Scott Lamond2Stuart Campbell3Geeta Nargund4Centre for Reproductive Medicine, Department of Obstetrics & Gynaecology, St. George's Hospital Medical School, Cranmer Terrace, University of London, London SW17 ORE, UKCentre for Reproductive Medicine, Department of Obstetrics & Gynaecology, St. George's Hospital Medical School, Cranmer Terrace, University of London, London SW17 ORE, UKCentre for Reproductive Medicine, Department of Obstetrics & Gynaecology, St. George's Hospital Medical School, Cranmer Terrace, University of London, London SW17 ORE, UKCentre for Reproductive Medicine, Department of Obstetrics & Gynaecology, St. George's Hospital Medical School, Cranmer Terrace, University of London, London SW17 ORE, UKCentre for Reproductive Medicine, Department of Obstetrics & Gynaecology, St. George's Hospital Medical School, Cranmer Terrace, University of London, London SW17 ORE, UKThe imprinting control region (ICR) located far upstream of the H19 gene, in conjunction with enhancers, modulates the transcription of Igf2 and H19 genes in an allele-specific manner. On paternal inheritance, the methylated ICR silences the H19 gene and indirectly facilitates transcription from the distant Igf2 promoter, whereas on the maternal chromosome the unmethylated ICR, together with enhancers, activates transcription of the H19 gene and thereby contributes to the repression of Igf2. This repression of maternal Igf2 has recently been postulated to be due to a chromatin boundary or insulator function of the unmethylated ICR. Central to the insulator model is the site-specific binding of a ubiquitous nuclear factor CTCF which exhibits remarkable flexibility in functioning as transcriptional activator or silencer. We suggest that the ICR positioned close to the enhancers in an episomal context might function as a transcriptional silencer by virtue of interaction of CTCF with its modifiers such as SIN3A and histone deacetylases. Furthermore, a localised folded chromatin structure resulting from juxtaposition of two disparate regulatory sequences (enhancer ICR) could be the mechanistic basis of ICR-mediated position-dependent (ICR-promoter) transcriptional repression in transgenic Drosophila.http://dx.doi.org/10.1100/tsw.2001.50 |
| spellingShingle | Subhasis Banerjee Alan Smallwood Scott Lamond Stuart Campbell Geeta Nargund Igf2/H19 Imprinting Control Region (ICR): An Insulator or a Position-Dependent Silencer? The Scientific World Journal |
| title | Igf2/H19 Imprinting Control Region (ICR): An Insulator or a Position-Dependent Silencer? |
| title_full | Igf2/H19 Imprinting Control Region (ICR): An Insulator or a Position-Dependent Silencer? |
| title_fullStr | Igf2/H19 Imprinting Control Region (ICR): An Insulator or a Position-Dependent Silencer? |
| title_full_unstemmed | Igf2/H19 Imprinting Control Region (ICR): An Insulator or a Position-Dependent Silencer? |
| title_short | Igf2/H19 Imprinting Control Region (ICR): An Insulator or a Position-Dependent Silencer? |
| title_sort | igf2 h19 imprinting control region icr an insulator or a position dependent silencer |
| url | http://dx.doi.org/10.1100/tsw.2001.50 |
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