Analysis of chromatin accessibility in human epidermis identifies putative barrier dysfunction-sensing enhancers.
Analysis of chromatin accessibility in human epidermis identifies putative barrier dysfunction-sensing enhancers.
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DOI：
10.1371/journal.pone.0184500
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Kopan R
中科院分区：
文献类型：
--
作者：
Lander JM;Supp DM;He H;Martin LJ;Chen X;Weirauch MT;Boyce ST;Kopan R
To identify putative gene regulatory regions that respond to epidermal injury, we mapped chromatin dynamics in a stratified human epidermis during barrier maturation and disruption. Engineered skin substitutes (ESS) cultured at the air-liquid interface were used as a model of developing human epidermis with incomplete barrier formation. The epidermal barrier stabilized following engraftment onto immunocompromised mice, and was compromised again upon injury. Modified formaldehyde-assisted isolation of regulatory elements (FAIRE) was used to identify accessible genomic regions characteristic of monolayer keratinocytes, ESS in vitro, grafted ESS, and tape-stripped ESS graft. We mapped differentiation- and maturation-associated changes in transcription factor binding sites enriched at each stage and observed overrepresentation of AP-1 gene family motifs in barrier-deficient samples. Transcription of TSLP, an important effector of immunological memory in response to allergen exposure, was dramatically elevated in our barrier-deficient samples. We identified dynamic DNA elements that correlated with TSLP induction and may contain enhancers that regulate TSLP. Two dynamic regions were located near the TSLP promoter and overlapped with allergy-associated SNPs rs17551370 and rs2289877, strongly implicating these loci in the regulation of TSLP expression in allergic disease. Additional dynamic chromatin regions ~250kb upstream of the TSLP promoter were found to be in high linkage disequilibrium with allergic disease SNPs. Taken together, these results define dynamic chromatin accessibility changes during epidermal development and dysfunction.
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影响因子：
3.7
作者：
Baye TM;Butsch Kovacic M;Biagini Myers JM;Martin LJ;Lindsey M;Patterson TL;He H;Ericksen MB;Gupta J;Tsoras AM;Lindsley A;Rothenberg ME;Wills-Karp M;Eissa NT;Borish L;Khurana Hershey GK
通讯作者：
Khurana Hershey GK
影响因子：
12.3
作者：
Bao X;Rubin AJ;Qu K;Zhang J;Giresi PG;Chang HY;Khavari PA
通讯作者：
Khavari PA
DOI：
10.1084/jem.20082242
发表时间：
2009-05-11
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Briot A;Deraison C;Lacroix M;Bonnart C;Robin A;Besson C;Dubus P;Hovnanian A
通讯作者：
Hovnanian A
影响因子：
14.2
作者：
Ferreira, Manuel A. R.;Matheson, Melanie C.;Tang, Clara S.;Granell, Raquel;Ang, Wei;Hui, Jennie;Kiefer, Amy K.;Duffy, David L.;Baltic, Svetlana;Danoy, Patrick;Bui, Minh;Price, Loren;Sly, Peter D.;Eriksson, Nicholas;Madden, Pamela A.;Abramson, Michael J.;Holt, Patrick G.;Heath, Andrew C.;Hunter, Michael;Musk, Bill;Robertson, Colin F.;Le Souef, Peter;Montgomery, Grant W.;Henderson, A. John;Tung, Joyce Y.;Dharmage, Shyamali C.;Brown, Matthew A.;James, Alan;Thompson, Philip J.;Pennell, Craig;Martin, Nicholas G.;Evans, David M.;Hinds, David A.;Hopper, John L.
通讯作者：
Hopper, John L.
DOI：
10.1038/nrg3454
发表时间：
2013-06
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
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