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Monoallelic Chromatin Conformation Flanking Long-Range Silenced Domains in Cancer-Derived and Normal Cells

Epigenetic inactivation of chromatin plays an important role in determining cell phenotype in both normal and cancer cells, but our knowledge is still incomplete with respect to any potential monoallelic nature of the phenomenon. We have genotyped DNA isolated from chromatin of two colorectal cancer...

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Autores principales: Di Paola, Domenic, Raelson, John, Rampakakis, Emmanouil, Basik, Mark, Zannis-Hadjopoulos, Maria, Bradley, W. Edward C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3655995/
https://www.ncbi.nlm.nih.gov/pubmed/23696799
http://dx.doi.org/10.1371/journal.pone.0063190
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author Di Paola, Domenic
Raelson, John
Rampakakis, Emmanouil
Basik, Mark
Zannis-Hadjopoulos, Maria
Bradley, W. Edward C.
author_facet Di Paola, Domenic
Raelson, John
Rampakakis, Emmanouil
Basik, Mark
Zannis-Hadjopoulos, Maria
Bradley, W. Edward C.
author_sort Di Paola, Domenic
collection PubMed
description Epigenetic inactivation of chromatin plays an important role in determining cell phenotype in both normal and cancer cells, but our knowledge is still incomplete with respect to any potential monoallelic nature of the phenomenon. We have genotyped DNA isolated from chromatin of two colorectal cancer-derived lines and a culture of normal human intestinal epithelial cells (HIEC), which was immunoprecipitated with antibodies to acetylated vs. methylated histone H3K9, and presented the data as B allele frequency differences over multiple single-nucleotide polymorphism (SNP) moving window averages. [B allele is an arbitrary term defined as one of the two alleles at any given SNP, named A and B]. Three different validation tests confirmed that peaks exhibiting differences represented monoallelic domains. These complementary tests confirmed the following: 1) genes in the regions of high B allele frequency difference were expressed monoallelically; 2) in normal cells all five imprinting control regions which carried heterozygous SNPs were characterized by B allele difference peaks; and 3) the haplotypes in the B allele difference peaks were faithfully maintained in the chromatin immunoprecipitated with the respective antibodies. In both samples most of the monoallelic domains were found at the boundaries between regions of open and closed chromatin. With respect to the cancer line, this supports the established concept of conformation spreading, but the results from the normal cells were unexpected. Since these cells were polyclonal, the monoallelic structures were probably not determined by random choice as occurs in X-inactivation, so we propose that epigenetic inactivation in some domains may be heritable and polymorphic in normal human cells.
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spelling pubmed-36559952013-05-21 Monoallelic Chromatin Conformation Flanking Long-Range Silenced Domains in Cancer-Derived and Normal Cells Di Paola, Domenic Raelson, John Rampakakis, Emmanouil Basik, Mark Zannis-Hadjopoulos, Maria Bradley, W. Edward C. PLoS One Research Article Epigenetic inactivation of chromatin plays an important role in determining cell phenotype in both normal and cancer cells, but our knowledge is still incomplete with respect to any potential monoallelic nature of the phenomenon. We have genotyped DNA isolated from chromatin of two colorectal cancer-derived lines and a culture of normal human intestinal epithelial cells (HIEC), which was immunoprecipitated with antibodies to acetylated vs. methylated histone H3K9, and presented the data as B allele frequency differences over multiple single-nucleotide polymorphism (SNP) moving window averages. [B allele is an arbitrary term defined as one of the two alleles at any given SNP, named A and B]. Three different validation tests confirmed that peaks exhibiting differences represented monoallelic domains. These complementary tests confirmed the following: 1) genes in the regions of high B allele frequency difference were expressed monoallelically; 2) in normal cells all five imprinting control regions which carried heterozygous SNPs were characterized by B allele difference peaks; and 3) the haplotypes in the B allele difference peaks were faithfully maintained in the chromatin immunoprecipitated with the respective antibodies. In both samples most of the monoallelic domains were found at the boundaries between regions of open and closed chromatin. With respect to the cancer line, this supports the established concept of conformation spreading, but the results from the normal cells were unexpected. Since these cells were polyclonal, the monoallelic structures were probably not determined by random choice as occurs in X-inactivation, so we propose that epigenetic inactivation in some domains may be heritable and polymorphic in normal human cells. Public Library of Science 2013-05-16 /pmc/articles/PMC3655995/ /pubmed/23696799 http://dx.doi.org/10.1371/journal.pone.0063190 Text en © 2013 Di Paola et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Di Paola, Domenic
Raelson, John
Rampakakis, Emmanouil
Basik, Mark
Zannis-Hadjopoulos, Maria
Bradley, W. Edward C.
Monoallelic Chromatin Conformation Flanking Long-Range Silenced Domains in Cancer-Derived and Normal Cells
title Monoallelic Chromatin Conformation Flanking Long-Range Silenced Domains in Cancer-Derived and Normal Cells
title_full Monoallelic Chromatin Conformation Flanking Long-Range Silenced Domains in Cancer-Derived and Normal Cells
title_fullStr Monoallelic Chromatin Conformation Flanking Long-Range Silenced Domains in Cancer-Derived and Normal Cells
title_full_unstemmed Monoallelic Chromatin Conformation Flanking Long-Range Silenced Domains in Cancer-Derived and Normal Cells
title_short Monoallelic Chromatin Conformation Flanking Long-Range Silenced Domains in Cancer-Derived and Normal Cells
title_sort monoallelic chromatin conformation flanking long-range silenced domains in cancer-derived and normal cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3655995/
https://www.ncbi.nlm.nih.gov/pubmed/23696799
http://dx.doi.org/10.1371/journal.pone.0063190
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