Handle URI:
http://hdl.handle.net/10754/598296
Title:
Extensive Variation in Chromatin States Across Humans
Authors:
Kasowski, M.; Kyriazopoulou-Panagiotopoulou, S.; Grubert, F.; Zaugg, J. B.; Kundaje, A.; Liu, Y.; Boyle, A. P.; Zhang, Q. C.; Zakharia, F.; Spacek, D. V.; Li, J.; Xie, D.; Olarerin-George, A.; Steinmetz, L. M.; Hogenesch, J. B.; Kellis, M.; Batzoglou, S.; Snyder, M.
Abstract:
The majority of disease-associated variants lie outside protein-coding regions, suggesting a link between variation in regulatory regions and disease predisposition. We studied differences in chromatin states using five histone modifications, cohesin, and CTCF in lymphoblastoid lines from 19 individuals of diverse ancestry. We found extensive signal variation in regulatory regions, which often switch between active and repressed states across individuals. Enhancer activity is particularly diverse among individuals, whereas gene expression remains relatively stable. Chromatin variability shows genetic inheritance in trios, correlates with genetic variation and population divergence, and is associated with disruptions of transcription factor binding motifs. Overall, our results provide insights into chromatin variation among humans.
Citation:
Kasowski M, Kyriazopoulou-Panagiotopoulou S, Grubert F, Zaugg JB, Kundaje A, et al. (2013) Extensive Variation in Chromatin States Across Humans. Science 342: 750–752. Available: http://dx.doi.org/10.1126/science.1242510.
Publisher:
American Association for the Advancement of Science (AAAS)
Journal:
Science
Issue Date:
17-Oct-2013
DOI:
10.1126/science.1242510
PubMed ID:
24136358
PubMed Central ID:
PMC4075767
Type:
Article
ISSN:
0036-8075; 1095-9203
Sponsors:
Funded by grants from the NIH and Genetics Department, Stanford University, Vera Moulton Wall Center for Pulmonary Vascular Disease and NIH MSTP TG T32GM07205 (M. K.), the Siebel Scholars Foundation (S.-K.P.), the KAUST-Stanford Academic Excellence Alliance program (S.-K.P. and S. B.), the Swiss National Foundation, and the Janggen-Poehn Foundation (J.B.Z.). Data sets are available at the Gene Expression Omnibus (GEO) database with accession no. GSE50893. We thank S. Montgomery, W. Huber, C. Bustamante, H. Tang, S. Anders, G. Euskirchen, B. Altshuler, M. Eaton, and L. Ward. M. S. is a founder and member of the science advisory board for Personalis and a science advisory board member for Genapsys and AxioMx. S. B. is a founder and advisor for DNAnexus and serves on the advisory boards of 23andMe and Eve Biomedical. Genotype calls and BAM files with mapped sequencing reads for the San individuals are available through a data access agreement for transfer of genetic data by contacting M.S.
Appears in Collections:
Publications Acknowledging KAUST Support

Full metadata record

DC FieldValue Language
dc.contributor.authorKasowski, M.en
dc.contributor.authorKyriazopoulou-Panagiotopoulou, S.en
dc.contributor.authorGrubert, F.en
dc.contributor.authorZaugg, J. B.en
dc.contributor.authorKundaje, A.en
dc.contributor.authorLiu, Y.en
dc.contributor.authorBoyle, A. P.en
dc.contributor.authorZhang, Q. C.en
dc.contributor.authorZakharia, F.en
dc.contributor.authorSpacek, D. V.en
dc.contributor.authorLi, J.en
dc.contributor.authorXie, D.en
dc.contributor.authorOlarerin-George, A.en
dc.contributor.authorSteinmetz, L. M.en
dc.contributor.authorHogenesch, J. B.en
dc.contributor.authorKellis, M.en
dc.contributor.authorBatzoglou, S.en
dc.contributor.authorSnyder, M.en
dc.date.accessioned2016-02-25T13:18:11Zen
dc.date.available2016-02-25T13:18:11Zen
dc.date.issued2013-10-17en
dc.identifier.citationKasowski M, Kyriazopoulou-Panagiotopoulou S, Grubert F, Zaugg JB, Kundaje A, et al. (2013) Extensive Variation in Chromatin States Across Humans. Science 342: 750–752. Available: http://dx.doi.org/10.1126/science.1242510.en
dc.identifier.issn0036-8075en
dc.identifier.issn1095-9203en
dc.identifier.pmid24136358en
dc.identifier.doi10.1126/science.1242510en
dc.identifier.urihttp://hdl.handle.net/10754/598296en
dc.description.abstractThe majority of disease-associated variants lie outside protein-coding regions, suggesting a link between variation in regulatory regions and disease predisposition. We studied differences in chromatin states using five histone modifications, cohesin, and CTCF in lymphoblastoid lines from 19 individuals of diverse ancestry. We found extensive signal variation in regulatory regions, which often switch between active and repressed states across individuals. Enhancer activity is particularly diverse among individuals, whereas gene expression remains relatively stable. Chromatin variability shows genetic inheritance in trios, correlates with genetic variation and population divergence, and is associated with disruptions of transcription factor binding motifs. Overall, our results provide insights into chromatin variation among humans.en
dc.description.sponsorshipFunded by grants from the NIH and Genetics Department, Stanford University, Vera Moulton Wall Center for Pulmonary Vascular Disease and NIH MSTP TG T32GM07205 (M. K.), the Siebel Scholars Foundation (S.-K.P.), the KAUST-Stanford Academic Excellence Alliance program (S.-K.P. and S. B.), the Swiss National Foundation, and the Janggen-Poehn Foundation (J.B.Z.). Data sets are available at the Gene Expression Omnibus (GEO) database with accession no. GSE50893. We thank S. Montgomery, W. Huber, C. Bustamante, H. Tang, S. Anders, G. Euskirchen, B. Altshuler, M. Eaton, and L. Ward. M. S. is a founder and member of the science advisory board for Personalis and a science advisory board member for Genapsys and AxioMx. S. B. is a founder and advisor for DNAnexus and serves on the advisory boards of 23andMe and Eve Biomedical. Genotype calls and BAM files with mapped sequencing reads for the San individuals are available through a data access agreement for transfer of genetic data by contacting M.S.en
dc.publisherAmerican Association for the Advancement of Science (AAAS)en
dc.subject.meshGene Expression Regulationen
dc.titleExtensive Variation in Chromatin States Across Humansen
dc.typeArticleen
dc.identifier.journalScienceen
dc.identifier.pmcidPMC4075767en
dc.contributor.institutionDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.en
kaust.grant.programAcademic Excellence Alliance (AEA)en

Related articles on PubMed

All Items in KAUST are protected by copyright, with all rights reserved, unless otherwise indicated.