title: Allele-specific chromatin immunoprecipitation studies show genetic influence on chromatin state in human genome.
abstract: Several recent studies have shown a genetic influence on gene expression variation, including variation between the two chromosomes within an individual and variation between individuals at the population level. We hypothesized that genetic inheritance may also affect variation in chromatin states. To test this hypothesis, we analyzed chromatin states in 12 lymphoblastoid cells derived from two Centre d'Etude du Polymorphisme Humain families using an allele-specific chromatin immunoprecipitation (ChIP-on-chip) assay with Affymetrix 10K SNP chip. We performed the allele-specific ChIP-on-chip assays for the 12 lymphoblastoid cells using antibodies targeting at RNA polymerase II and five post-translation modified forms of the histone H3 protein. The use of multiple cell lines from the Centre d'Etude du Polymorphisme Humain families allowed us to evaluate variation of chromatin states across pedigrees. These studies demonstrated that chromatin state clustered by family. Our results support the idea that genetic inheritance can determine the epigenetic state of the chromatin as shown previously in model organisms. To our knowledge, this is the first demonstration in humans that genetics may be an important factor that influences global chromatin state mediated by histone modification, the hallmark of the epigenetic phenomena.
authors.affiliation: Laboratory of Population Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Mitsutaka
authors.initials: M
authors.lastname: Kadota
authors.forename: Howard H
authors.initials: HH
authors.lastname: Yang
authors.forename: Nan
authors.initials: N
authors.lastname: Hu
authors.forename: Chaoyu
authors.initials: C
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Hu
authors.forename: Philip R
authors.initials: PR
authors.lastname: Taylor
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Buetow
authors.forename: Maxwell P
authors.initials: MP
authors.lastname: Lee
mesh_terms: D000107:Acetylation; D000293:Adolescent; D000328:Adult; D000483:Alleles; D000918:Antibody Specificity / Q000235:genetics; D020029:Base Pairing / Q000235:genetics; D002648:Child; D002843:Chromatin / Q000235:genetics* / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation / Q000379:methods*; D016000:Cluster Analysis; D005260:Female; D015894:Genome, Human / Q000235:genetics*; D006657:Histones / Q000378:metabolism; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics; D008297:Male; D008875:Middle Aged; D025341:Principal Component Analysis; D011401:Promoter Regions, Genetic / Q000235:genetics
chemical_list: D002843:Chromatin; D006657:Histones