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Chromatin-Remodelling Complex NURF Is Essential for Differentiation of Adult Melanocyte Stem Cells


The melanocytes pigmenting the coat of adult mice derive from the melanocyte stem cell population residing in the permanent bulge area of the hair follicle. At each angen phase, melanocyte stem cells are stimulated to generate proliferative transient amplifying cells that migrate to the bulb of the follicle where they differentiate into mature melanin producing melanocytes, a processes involving MIcrophthalmia-associated Transcription Factor (MITF) the master regulator of the melanocyte lineage. We show that MITF associates with the NURF chromatin-remodelling factor in melanoma cells. NURF acts downstream of MITF in melanocytes and melanoma cells co-regulating gene expression in vitro. In vivo, mice lacking the NURF subunit Bptf in the melanocyte lineage show premature greying as they are unable to generate mature melanocytes from the adult stem cell population. We find that the melanocyte stem cells from these animals are abnormal and that once they are stimulated at anagen, Bptf is required to ensure the expression of melanocyte markers and their differentiation into mature adult melanocytes. Chromatin remodelling by NURF therefore appears to be essential for the transition of the transcriptionally quiescent stem cell to the differentiated state.


Vyšlo v časopise: Chromatin-Remodelling Complex NURF Is Essential for Differentiation of Adult Melanocyte Stem Cells. PLoS Genet 11(10): e32767. doi:10.1371/journal.pgen.1005555
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005555

Souhrn

The melanocytes pigmenting the coat of adult mice derive from the melanocyte stem cell population residing in the permanent bulge area of the hair follicle. At each angen phase, melanocyte stem cells are stimulated to generate proliferative transient amplifying cells that migrate to the bulb of the follicle where they differentiate into mature melanin producing melanocytes, a processes involving MIcrophthalmia-associated Transcription Factor (MITF) the master regulator of the melanocyte lineage. We show that MITF associates with the NURF chromatin-remodelling factor in melanoma cells. NURF acts downstream of MITF in melanocytes and melanoma cells co-regulating gene expression in vitro. In vivo, mice lacking the NURF subunit Bptf in the melanocyte lineage show premature greying as they are unable to generate mature melanocytes from the adult stem cell population. We find that the melanocyte stem cells from these animals are abnormal and that once they are stimulated at anagen, Bptf is required to ensure the expression of melanocyte markers and their differentiation into mature adult melanocytes. Chromatin remodelling by NURF therefore appears to be essential for the transition of the transcriptionally quiescent stem cell to the differentiated state.


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