Located at the interface between your body and its surrounding environment, your epidermis acts as a barrier against the entry of infectious agents and the loss of bodily fluids. At a microscopic level, the structures that provide the barrier function resemble bricks and mortar"""""""" with dead skin cells forming the bricks and lipids acting as the mortar. We investigated the role of the DNA binding protein KLF4 in directly regulating the process by which the epidermis establishes the barrier. Mice lacking KLF4 protein seem healthy at birth but die within 15 hours due to rapid water loss through their skin. To analyze the mechanism by which KLF4 regulates the development of barrier function we identified downstream targets of KLF4 genes which are turned on or off under the influence of KLF4. We identified these genes based on two complementary methods: cDNA microarrays and subtractive cloning. These targets encode proteins that regulate cell proliferation and major components of the cellular """"""""bricks"""""""". Ongoing research assigns these transcripts to regulatory pathways based on their expression and function in the epidermis.""""""""

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Intramural Research (Z01)
Project #
1Z01HG000180-01
Application #
6555943
Study Section
(GMBB)
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2001
Total Cost
Indirect Cost
Name
Human Genome Research
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Choi, Yeon Sook; Cheng, Jun; Segre, Julie et al. (2008) Generation and analysis of Elf5-LacZ mouse: unique and dynamic expression of Elf5 (ESE-2) in the inner root sheath of cycling hair follicles. Histochem Cell Biol 129:85-94
Grice, Elizabeth A; Kong, Heidi H; Renaud, Gabriel et al. (2008) A diversity profile of the human skin microbiota. Genome Res 18:1043-50
de Guzman Strong, Cristina; Segre, Julia A (2008) Navigating the genome. J Cell Sci 121:921-3
Kharas, Michael G; Yusuf, Isharat; Scarfone, Vanessa M et al. (2007) KLF4 suppresses transformation of pre-B cells by ABL oncogenes. Blood 109:747-55
List, Karin; Currie, Brooke; Scharschmidt, Tiffany C et al. (2007) Autosomal ichthyosis with hypotrichosis syndrome displays low matriptase proteolytic activity and is phenocopied in ST14 hypomorphic mice. J Biol Chem 282:36714-23
Teng, Andy; Nair, Mahalakshmi; Wells, Julie et al. (2007) Strain-dependent perinatal lethality of Ovol1-deficient mice and identification of Ovol2 as a downstream target of Ovol1 in skin epidermis. Biochim Biophys Acta 1772:89-95
Feinberg, Mark W; Wara, Akm Khyrul; Cao, Zhuoxiao et al. (2007) The Kruppel-like factor KLF4 is a critical regulator of monocyte differentiation. EMBO J 26:4138-48
Segre, Julia A (2006) Epidermal barrier formation and recovery in skin disorders. J Clin Invest 116:1150-8
Djalilian, Ali R; McGaughey, David; Patel, Satyakam et al. (2006) Connexin 26 regulates epidermal barrier and wound remodeling and promotes psoriasiform response. J Clin Invest 116:1243-53
Segre, Julia A (2006) Epidermal differentiation complex yields a secret: mutations in the cornification protein filaggrin underlie ichthyosis vulgaris. J Invest Dermatol 126:1202-4

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