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Penn study on skin formation suggests strategies to fight skin cancer
Date:12/6/2010

PHILADELPHIA - In a study published in the journal Developmental Cell, Sarah Millar PhD, professor of Dermatology and Cell & Developmental Biology at the University of Pennsylvania School of Medicine, and colleagues demonstrate that a pair of enzymes called HDACs are critical to the proper formation of mammalian skin.

The findings, Millar says, not only provide information about the molecular processes underlying skin development, they also suggest a potential anticancer strategy. "Inhibition of these HDAC enzymes might be able to shut down the growth of tumors that contain cells resembling those in embryonic skin," she says.

Acting as a barrier to infection and dehydration, the outermost layer of the skin, called the epidermis, is a stratified structure in which progenitor stem cells in the bottommost layer continuously divide to replenish the cells in the upper layers that are lost as skin cells slough off. The origin of this structure is a single cell layer called surface ectoderm that covers vertebrate embryos.

Millar's team is interested in how surface ectoderm becomes epidermis. They decided to focus on enzymes that control gene expression by regulating the accessibility of chromatin - the DNA and protein structure in which genes reside. Within the chromatin, DNA is wound around proteins known as histones. The degree of compaction of this structure influences whether or not genes are expressed. Genes in tightly wound chromatin areas are generally inaccessible and suppressed, whereas those in "open" or loosely packed areas can be activated.

HDACs remove chemical modifications known as acetyl groups from histones, resulting in a compact and repressive chromatin environment. Previous evidence had suggested a possible role for histone acetylation in regulating epidermal development, but its exact functions were unclear.

Skin Essentials

Penn MD/PhD student Matthew LeBoeuf, the lead
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert  

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