Abstract
The extent to which variation in chromatin structure and transcription factor binding may influence gene expression, and thus underlie or contribute to variation in phenotype, is unknown. To address this question, we cataloged both individual-to-individual variation and differences between homologous chromosomes within the same individual (allele-specific variation) in chromatin structure and transcription factor binding in lymphoblastoid cells derived from individuals of geographically diverse ancestry. Ten percent of active chromatin sites were individual-specific; a similar proportion were allele-specific. Both individual-specific and allele-specific sites were commonly transmitted from parent to child, which suggests that they are heritable features of the human genome. Our study shows that heritable chromatin status and transcription factor binding differ as a result of genetic variation and may underlie phenotypic variation in humans.
MeSH Terms
Alleles
Binding Sites
Blacks
CCCTC-Binding Factor
Cell Line
Chromatin/chemistry,genetics,metabolism
Chromatin Immunoprecipitation
Chromosomes, Human/genetics,metabolism
Chromosomes, Human, X/genetics,metabolism
Deoxyribonuclease I/metabolism
Female
Gene Expression Regulation
Genetic Variation
Humans
Male
Nuclear Family
Polymorphism, Single Nucleotide
Protein Binding
Regulatory Elements, Transcriptional
Repressor Proteins/metabolism
Sequence Analysis, DNA
Transcription Factors/metabolism
Whites
X Chromosome Inactivation
Chemicals
CCCTC-Binding Factor
CTCF protein, human
Chromatin
Repressor Proteins
Transcription Factors
Deoxyribonuclease I
Authors & Affiliations
18 authors, click to expand affiliations / ORCID
McDaniell Ryan
Center for Systems and Synthetic Biology, Institute for Cellular and Molecular Biology, Section of Molecular Genetics and Microbiology, University of Texas, Austin, TX 78712, USA.
Lee Bum-Kyu
Song Lingyun
Liu Zheng
Boyle Alan P
Erdos Michael R
Scott Laura J
Morken Mario A
Kucera Katerina S
Battenhouse Anna
Keefe Damian
Collins Francis S
Willard Huntington F
Lieb Jason D
Furey Terrence S
Crawford Gregory E
Iyer Vishwanath R
Birney Ewan
References (16)
16 references, click to expand
-
Allelic variation in human gene expression.
Science. 2002 Aug 16;297(5584):1143
PMID: 12183620
-
The resolution of the genetics of gene expression.
Hum Mol Genet. 2009 Oct 15;18(R2):R211-5
PMID: 19808798
-
Genomic imprinting: CTCF protects the boundaries.
Curr Biol. 2004 Apr 6;14(7):R284-6
PMID: 15062124
-
Genetic analysis of genome-wide variation in human gene expression.
Nature. 2004 Aug 12;430(7001):743-7
PMID: 15269782
-
The chromatin structure of specific genes: I. Evidence for higher order domains of defined DNA sequence.
Cell. 1979 Apr;16(4):797-806
PMID: 455449
-
Nuclease hypersensitive sites in chromatin.
Annu Rev Biochem. 1988;57:159-97
PMID: 3052270
-
How imprinting centres work.
Cytogenet Genome Res. 2006;113(1-4):81-9
PMID: 16575166
-
Analysis of the vertebrate insulator protein CTCF-binding sites in the human genome.
Cell. 2007 Mar 23;128(6):1231-45
PMID: 17382889
-
Allele-specific chromatin immunoprecipitation studies show genetic influence on chromatin state in human genome.
PLoS Genet. 2007 May 18;3(5):e81
PMID: 17511522
-
Genetics and epigenetics of the multifunctional protein CTCF.
Curr Top Dev Biol. 2008;80:337-60
PMID: 17950379
-
The potential role of epigenomic dysregulation in complex human disease.
Trends Genet. 2007 Nov;23(11):588-95
PMID: 17953999
-
Extreme clonality in lymphoblastoid cell lines with implications for allele specific expression analyses.
PLoS One. 2008;3(8):e2966
PMID: 18698422
-
CTCF: master weaver of the genome.
Cell. 2009 Jun 26;137(7):1194-211
PMID: 19563753
-
Digital RNA allelotyping reveals tissue-specific and allele-specific gene expression in human.
Nat Methods. 2009 Aug;6(8):613-8
PMID: 19620972
-
Genetics of human gene expression: mapping DNA variants that influence gene expression.
Nat Rev Genet. 2009 Sep;10(9):595-604
PMID: 19636342
-
High-throughput screening for evidence of association by using mass spectrometry genotyping on DNA pools.
Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):16928-33
PMID: 12482934