Transcriptional activation of a subset of hair keratin genes by the NF-κB effector p65/RelA

Michal Gilon, Noa Sher, Shulamit Cohen, Uri Gat*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


The hair follicle is an intricate miniature organ dedicated to the production of the structural hair fiber, which is largely composed of hair keratin (HK) proteins. Many developmental pathways contribute to hair follicle development; however, the molecular control of HK genes is still far from being resolved. Because the nuclear factor (NF)-κB pathway is known to be involved in the morphogenesis of the hair follicle, we explored the possibility that it may also regulate HK expression. To this end, we analyzed the effect of p65/RelA, an NF-κB effector, on HK regulatory regions using transient transfections into tissue culture cells. Reporter assays on cells transfected with HK promoter constructs and real-time polymerase chain reaction analysis of endogenous HK gene activity demonstrated that p65 induces transcriptional activation of several HK genes of human and mouse origin, primarily that of acidic hair keratin 5 (Ha5). Focusing on the highly responsive human Ha5 gene, we defined the major NF-κB/RelA binding sites in its regulatory region and showed the direct binding of p65 to these sites using gel shift assays. We further show, using immunohistochemistry on human hair follicle sections, that p65 is co-expressed with HKs in the hair shaft compartment and may thus be the effector that mediates the NF-κB pathway's activity, which recently was genetically demonstrated to be active in the same region. Thus, we provide evidence for a previously unknown function of NF-κB in hair formation - direct activation of HK target genes - a function that may shed light on some of the symptoms of ectodermal dysplasias.

Original languageAmerican English
Pages (from-to)518-530
Number of pages13
Issue number5
StatePublished - Jun 2008

Bibliographical note

Funding Information:
Acknowledgments Our thanks to Dr. Lutz Langbein of the German Cancer Research Center in Heidelberg for his generosity in kind gifts of antibodies against HKs and to Dr. Eli Pikarsky and members of his laboratory in the Hebrew University Hadassah Medical School for help in immunostaining of human skin sections. We also thank Eli Raveh of the Gat laboratory for his help with figure preparation. This work was supported by grant # 2005197 from the United States—Israel Binational Science Foundation.


  • Ectodermal dysplasia
  • Hair follicle
  • Hair keratins
  • Hair shaft
  • NF-κB pathway
  • Skin
  • Transcriptional activation
  • p65/RelA


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