In a discovery important to understanding how cells are born and proliferate, HMS researchers have uncovered the mechanism by which an essential regulatory enzyme directs the development and differentiation of skin pigment cells.
The study, published in the June 11 issue of Cell, focused on interactions between several key molecules in the pathway leading to the creation and proliferation of mature pigment cells, called melanocytes. At one end of this pathway are microRNAs, short segments of genetic material that affect gene expression and are active in cell development, differentiation and tumor growth. The creation and maturation of microRNAs depends on the processing enzyme DICER.
David E. Fisher, the Edward Wigglesworth professor of dermatology at HMS and Massachusetts General Hospital and head of the hospital’s Dermatology Department, and research fellow Carmit Levy led a team in identifying the mechanism in melanocytes that controls DICER expression. They discovered that while DICER was regulating the production of microRNAs, a protein specific to melanocytes was regulating the expression of DICER.
“In melanocytes, we observed that expression of DICER is controlled by a melanocyte-specific ‘master regulator’ transcription factor called MITF,” said Fisher. MITF acts as a master regulator of melanocyte development and is targeted by several critical signaling pathways. Fisher and his colleagues showed that MITF also directly induces DICER expression during melanocyte differentiation.
This finding may have implications for treating diseases like cancer. MITF mutations are present in some human skin cancers and changes in melanocyte survival through the control of DICER may contribute to tumor survival.
Fisher said that DICER is likely regulated by analogous proteins in other cell types in the body, not just by the melanocyte-specific MITF. “We hypothesize that other cell types may use their own specific transcription factors to control DICER expression during their own differentiation.”
The next steps for Fisher and his colleagues are to identify specific microRNAs that DICER processes during melanocyte differentiation. He hopes that these results will spur other investigators to examine whether DICER is regulated during differentiation in other cell types.
For more information, students may contact David Fisher at dfisher3@partners.org.
Conflict Disclosure: The authors declare no conflicts of interest.
Funding Sources: The National Institutes of Health; the authors are solely responsible for the content of this work.
