TY  - JOUR
AB  - Lineage-specific differentiation programs are activated by epigenetic changes in chromatin structure. Melanin-producing melanocytes maintain a gene expression program ensuring appropriate enzymatic conversion of metabolites into the pigment, melanin, and transfer to surrounding cells. During neuroectodermal development, SMARCA4 (BRG1), the catalytic subunit of SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complexes, is essential for lineage specification. SMARCA4 is also required for development of multipotent neural crest precursors into melanoblasts, which differentiate into pigment-producing melanocytes. In addition to the catalytic domain, SMARCA4 and several SWI/SNF subunits contain bromodomains which are amenable to pharmacological inhibition. We investigated the effects of pharmacological inhibitors of SWI/SNF bromodomains on melanocyte differentiation. Strikingly, treatment of murine melanoblasts and human neonatal epidermal melanocytes with selected bromodomain inhibitors abrogated melanin synthesis and visible pigmentation. Using functional genomics, iBRD9, a small molecule selective for the bromodomain of BRD9 was found to repress pigmentation-specific gene expression. Depletion of BRD9 confirmed a requirement for expression of pigmentation genes in the differentiation program from melanoblasts into pigmented melanocytes and in melanoma cells. Chromatin immunoprecipitation assays showed that iBRD9 disrupts the occupancy of BRD9 and the catalytic subunit SMARCA4 at melanocyte-specific loci. These data indicate that BRD9 promotes melanocyte pigmentation whereas pharmacological inhibition of BRD9 is repressive.
AU  - Basuroy, T.*
AU  - Dreier, M.*
AU  - Baum, C.*
AU  - Blomquist, T.*
AU  - Trumbly, R.*
AU  - Filipp, F.V.
AU  - de la Serna, I.L.*
C1  - 66392
C2  - 53165
SP  - 19-32
TI  - Epigenetic and pharmacological control of pigmentation via Bromodomain Protein 9 (BRD9).
JO  - Pigment Cell Melanoma Res.
VL  - 36
IS  - 1
PY  - 2023
SN  - 1755-1471
ER  - 

TY  - JOUR
AB  - The mouse tail has an important role in the study of melanogenesis, because mouse tail skin can be used to model human skin pigmentation. To better understand the development of melanocytes in the mouse tail, we cloned two dominant ENU-generated mutations of the Adamts9 gene, Und3 and Und4, which cause an unpigmented ring of epidermis in the middle of the tail, but do not alter pigmentation in the rest of the mouse. Adamts9 encodes a widely expressed zinc metalloprotease with thrombospondin type 1 repeats with few known substrates. Melanocytes are lost in the Adamts9 mutant tail epidermis at a relatively late stage of development, around E18.5. Studies of our Adamts9 conditional allele suggest that there is a melanocyte cell-autonomous requirement for Adamts9. In addition, we used a proteomics approach, TAILS N-terminomics, to identify new Adamts9 candidate substrates in the extracellular matrix of the skin. The tail phenotype of Adamts9 mutants is strikingly similar to the unpigmented trunk belt in Adamts20 mutants, which suggests a particular requirement for Adamts family activity at certain positions along the anteriorposterior axis.
AU  - Tharmarajah, G.*
AU  - Eckhard, U.*
AU  - Jain, F.*
AU  - Marino, G.*
AU  - Prudova, A.*
AU  - Urtatiz, O.*
AU  - Fuchs, H.
AU  - Hrabě de Angelis, M.
AU  - Overall, C.M.*
AU  - van Raamsdonk, C.D.*
C1  - 53554
C2  - 44632
CY  - 111 River St, Hoboken 07030-5774, Nj Usa
SP  - 693-707
TI  - Melanocyte development in the mouse tail epidermis requires the Adamts9 metalloproteinase.
JO  - Pigment Cell Melanoma Res.
VL  - 31
IS  - 6
PB  - Wiley
PY  - 2018
SN  - 1755-1471
ER  - 

TY  - JOUR
AU  - Ziegler, I.
C1  - 22297
C2  - 21101
SP  - 172-182
TI  - The Pteridine Pathway in Zebrafish : Regulation and Specification during the Determination of Neural Crest Cell-Fate.
JO  - Pigment Cell Melanoma Res.
VL  - 16
PY  - 2003
SN  - 1755-1471
ER  -