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

Dana Koludrovic1, Patrick Laurette2, Thomas Strub3

  • 1Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, Illkirch, France; Beaston Institute for Cancer Research, Glasgow, United Kingdom.

Plos Genetics
|October 7, 2015
PubMed

Insights

The Bromodomain PHD Transcripion Factor (BPTF) is crucial for melanocyte development and pigment production. BPTF regulates gene expression in melanocytes, and its absence leads to premature greying in mice.

Area of Science:

  • Cell Biology
  • Genetics
  • Dermatology

Background:

  • The Microphthalmia-associated Transcription Factor (MITF) is a key regulator of melanocyte and melanoma cell functions.
  • Chromatin remodeling plays a significant role in regulating gene expression in various cell types, including melanocytes.

Purpose of the Study:

  • To investigate the role of the NURF chromatin-remodeling factor, specifically the BPTF subunit, in melanocyte and melanoma physiology.
  • To elucidate the functional relationship between MITF and BPTF in regulating melanocyte gene expression and development.

Main Methods:

  • Short hairpin RNA (shRNA)-mediated silencing of BPTF in melanoma cell lines and melanocytes.
  • Comparative RNA sequencing (RNA-seq) to analyze gene expression changes.
  • Somatic inactivation of Bptf in murine melanoblasts in vivo.
  • Analysis of melanocyte stem cell (MSC) populations, transient amplifying cells (TACs), and coat pigmentation in Bptf-mutant mice.

Main Results:

  • BPTF is essential for the survival and function of melanoma cell lines and normal melanocytes in vitro.
  • MITF and BPTF co-regulate overlapping gene expression programs critical for melanocyte function.
  • In vivo inactivation of Bptf in melanoblasts impairs their proliferation, migration, and morphology.
  • Bptf-mutant mice exhibit premature greying due to defects in adult melanocyte stem cell activation and differentiation, resulting in a failure to produce pigmented melanocytes.

Conclusions:

  • BPTF is indispensable for the reactivation of the melanocyte gene expression program during anagen.
  • BPTF is required for the normal proliferation of transient amplifying cells and their differentiation into mature, melanin-producing melanocytes.
  • Dysregulation of BPTF leads to a transcriptionally repressed chromatin state in melanocyte stem cells, preventing proper melanocyte development and pigmentation.

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