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The epigenetic control of E-box and Myc-dependent chromatin modifications regulate the licensing of lamin B2 origin during cell cycle
Recent genome-wide mapping of the mammalian replication origins has suggested the role of transcriptional regulatory elements in origin activation. However, the nature of chromatin modifications associated with such trans-factors or epigenetic marks imprinted on cis-elements during the spatio-tempor...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3467044/ https://www.ncbi.nlm.nih.gov/pubmed/22772991 http://dx.doi.org/10.1093/nar/gks617 |
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author | Swarnalatha, Manickavinayaham Singh, Anup Kumar Kumar, Vijay |
author_facet | Swarnalatha, Manickavinayaham Singh, Anup Kumar Kumar, Vijay |
author_sort | Swarnalatha, Manickavinayaham |
collection | PubMed |
description | Recent genome-wide mapping of the mammalian replication origins has suggested the role of transcriptional regulatory elements in origin activation. However, the nature of chromatin modifications associated with such trans-factors or epigenetic marks imprinted on cis-elements during the spatio-temporal regulation of replication initiation remains enigmatic. To unveil the molecular underpinnings, we studied the human lamin B2 origin that spatially overlaps with TIMM 13 promoter. We observed an early G(1)-specific occupancy of c-Myc that facilitated the loading of mini chromosome maintenance protein (MCM) complex during subsequent mid-G(1) phase rather stimulating TIMM 13 gene expression. Investigations on the Myc-induced downstream events suggested a direct interaction between c-Myc and histone methyltransferase mixed-lineage leukemia 1 that imparted histone H3K4me3 mark essential for both recruitment of acetylase complex HBO1 and hyperacetylation of histone H4. Contemporaneously, the nucleosome remodeling promoted the loading of MCM proteins at the origin. These chromatin modifications were under the tight control of active demethylation of E-box as evident from methylation profiling. The active demethylation was mediated by the Ten-eleven translocation (TET)-thymine DNA glycosylase-base excision repair (BER) pathway, which facilitated spatio-temporal occupancy of Myc. Intriguingly, the genome-wide 43% occurrence of E-box among the human origins could support our hypothesis that epigenetic control of E-box could be a molecular switch for the licensing of early replicating origins. |
format | Online Article Text |
id | pubmed-3467044 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-34670442012-10-10 The epigenetic control of E-box and Myc-dependent chromatin modifications regulate the licensing of lamin B2 origin during cell cycle Swarnalatha, Manickavinayaham Singh, Anup Kumar Kumar, Vijay Nucleic Acids Res Genome Integrity, Repair and Replication Recent genome-wide mapping of the mammalian replication origins has suggested the role of transcriptional regulatory elements in origin activation. However, the nature of chromatin modifications associated with such trans-factors or epigenetic marks imprinted on cis-elements during the spatio-temporal regulation of replication initiation remains enigmatic. To unveil the molecular underpinnings, we studied the human lamin B2 origin that spatially overlaps with TIMM 13 promoter. We observed an early G(1)-specific occupancy of c-Myc that facilitated the loading of mini chromosome maintenance protein (MCM) complex during subsequent mid-G(1) phase rather stimulating TIMM 13 gene expression. Investigations on the Myc-induced downstream events suggested a direct interaction between c-Myc and histone methyltransferase mixed-lineage leukemia 1 that imparted histone H3K4me3 mark essential for both recruitment of acetylase complex HBO1 and hyperacetylation of histone H4. Contemporaneously, the nucleosome remodeling promoted the loading of MCM proteins at the origin. These chromatin modifications were under the tight control of active demethylation of E-box as evident from methylation profiling. The active demethylation was mediated by the Ten-eleven translocation (TET)-thymine DNA glycosylase-base excision repair (BER) pathway, which facilitated spatio-temporal occupancy of Myc. Intriguingly, the genome-wide 43% occurrence of E-box among the human origins could support our hypothesis that epigenetic control of E-box could be a molecular switch for the licensing of early replicating origins. Oxford University Press 2012-10 2012-07-05 /pmc/articles/PMC3467044/ /pubmed/22772991 http://dx.doi.org/10.1093/nar/gks617 Text en © The Author(s) 2012. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Genome Integrity, Repair and Replication Swarnalatha, Manickavinayaham Singh, Anup Kumar Kumar, Vijay The epigenetic control of E-box and Myc-dependent chromatin modifications regulate the licensing of lamin B2 origin during cell cycle |
title | The epigenetic control of E-box and Myc-dependent chromatin modifications regulate the licensing of lamin B2 origin during cell cycle |
title_full | The epigenetic control of E-box and Myc-dependent chromatin modifications regulate the licensing of lamin B2 origin during cell cycle |
title_fullStr | The epigenetic control of E-box and Myc-dependent chromatin modifications regulate the licensing of lamin B2 origin during cell cycle |
title_full_unstemmed | The epigenetic control of E-box and Myc-dependent chromatin modifications regulate the licensing of lamin B2 origin during cell cycle |
title_short | The epigenetic control of E-box and Myc-dependent chromatin modifications regulate the licensing of lamin B2 origin during cell cycle |
title_sort | epigenetic control of e-box and myc-dependent chromatin modifications regulate the licensing of lamin b2 origin during cell cycle |
topic | Genome Integrity, Repair and Replication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3467044/ https://www.ncbi.nlm.nih.gov/pubmed/22772991 http://dx.doi.org/10.1093/nar/gks617 |
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