Novel p63 target genes involved in paracrine signaling and keratinocyte differentiation.
Novel p63 target genes involved in paracrine signaling and keratinocyte differentiation.
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DOI：
10.1038/cddis.2010.49
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发表时间：
2010
影响因子：
9
通讯作者：
中科院分区：
文献类型：
--
作者：
转录因子p63是正常表皮屏障形成和维持所必需的。在此，我们使用染色质免疫沉淀结合DNA测序来鉴定参与正常人表皮角质形成细胞（NHEKs）生长和分化的新型p63靶基因。我们确定了超过2000个与p63结合的基因组位点，其中82个也在NHEK中受p63的转录调控。通过发现白细胞介素-1-α作为p63靶基因，我们确定p63是上皮-间充质串扰的调节因子。此外，三维器官型共培养揭示了TCF 7 L1，另一种新的p63靶基因，作为表皮增殖和分化的调节因子，提供了一种p63维持基底表皮细胞增殖潜力的机制。新靶基因的发现将p63与表皮发育所需的多种信号传导途径联系起来，包括调节旁分泌信号传导至增殖潜能。通过本研究鉴定了一些新的p63靶基因，进一步深入了解了p63调控表皮细胞生长和分化的机制。
The transcription factor p63 is required for proper epidermal barrier formation and maintenance. Herein, we used chromatin immunoprecipitation coupled with DNA sequencing to identify novel p63 target genes involved in normal human epidermal keratinocyte (NHEKs) growth and differentiation. We identified over 2000 genomic sites bound by p63, of which 82 were also transcriptionally regulated by p63 in NHEKs. Through the discovery of interleukin-1-α as a p63 target gene, we identified that p63 is a regulator of epithelial–mesenchymal crosstalk. Further, three-dimensional organotypic co-cultures revealed TCF7L1, another novel p63 target gene, as a regulator of epidermal proliferation and differentiation, providing a mechanism by which p63 maintains the proliferative potential of basal epidermal cells. The discovery of new target genes links p63 to diverse signaling pathways required for epidermal development, including regulation of paracrine signaling to proliferative potential. Further mechanistic insight into p63 regulation of epidermal cell growth and differentiation is provided by the identification of a number of novel p63 target genes in this study.
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影响因子：
64.8
作者：
Mills, AA;Zheng, BH;Bradley, A
通讯作者：
Bradley, A
影响因子：
4.8
作者：
Helton, ES;Zhu, JH;Chen, XB
通讯作者：
Chen, XB
影响因子：
6.5
作者：
MaasSzabowski, N;Fusenig, NE
通讯作者：
Fusenig, NE
DOI：
10.1164/ajrccm/142.6_pt_2.s7
发表时间：
1990-12-01
期刊：
AMERICAN REVIEW OF RESPIRATORY DISEASE
影响因子：
--
作者：
AARONSON, SA;RUBIN, JS;KRAUS, MH
通讯作者：
KRAUS, MH
影响因子：
10.5
作者：
Koster, MI;Kim, S;Roop, DR
通讯作者：
Roop, DR