Zaugg, J. B.
Boyle, A. P.
Zhang, Q. C.
Spacek, D. V.
Steinmetz, L. M.
Hogenesch, J. B.
Permanent link to this recordhttp://hdl.handle.net/10754/598296
MetadataShow full item record
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.
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.
SponsorsFunded 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.
PubMed Central IDPMC4075767
CollectionsPublications Acknowledging KAUST Support
- Cohesin mediates chromatin interactions that regulate mammalian β-globin expression.
- Authors: Chien R, Zeng W, Kawauchi S, Bender MA, Santos R, Gregson HC, Schmiesing JA, Newkirk DA, Kong X, Ball AR Jr, Calof AL, Lander AD, Groudine MT, Yokomori K
- Issue date: 2011 May 20
- Genome-wide studies of CCCTC-binding factor (CTCF) and cohesin provide insight into chromatin structure and regulation.
- Authors: Lee BK, Iyer VR
- Issue date: 2012 Sep 7
- Insulators and domains of gene expression.
- Authors: Ali T, Renkawitz R, Bartkuhn M
- Issue date: 2016 Apr
- Cohesin is positioned in mammalian genomes by transcription, CTCF and Wapl.
- Authors: Busslinger GA, Stocsits RR, van der Lelij P, Axelsson E, Tedeschi A, Galjart N, Peters JM
- Issue date: 2017 Apr 27
- Topoisomerase II beta interacts with cohesin and CTCF at topological domain borders.
- Authors: Uusküla-Reimand L, Hou H, Samavarchi-Tehrani P, Rudan MV, Liang M, Medina-Rivera A, Mohammed H, Schmidt D, Schwalie P, Young EJ, Reimand J, Hadjur S, Gingras AC, Wilson MD
- Issue date: 2016 Aug 31