Year: 2012
Type: article
Abstract: Studies of coat color mutants have greatly contributed to the discovery of genes that regulate melanocyte development and function. Here, we generated Yy1 conditional knockout mice in the melanocyte-lineage and observed profound melanocyte deficiency and premature gray hair, similar to the loss of melanocytes in human piebaldism and Waardenburg syndrome. Although YY1 is a ubiquitous transcription factor, YY1 interacts with M-MITF, the Waardenburg Syndrome IIA gene and a master transcriptional regulator of melanocytes. YY1 cooperates with M-MITF in regulating the expression of piebaldism gene KIT and multiple additional pigmentation genes. Moreover, ChIP-seq identified genome-wide YY1 targets in the melanocyte lineage. These studies mechanistically link genes implicated in human conditions of melanocyte deficiency and reveal how a ubiquitous factor (YY1) gains lineage-specific functions by co-regulating gene expression with a lineage-restricted factor (M-MITF)-a general mechanism which may confer tissue-specific gene expression in multiple lineages.
Source: PLoS Genetics
Institutions: Harvard University, Massachusetts General Hospital, University of California, San Francisco, Boston Children's Hospital, Massachusetts Institute of Technology, Harvard–MIT Division of Health Sciences and Technology, Koch Institute for Integrative Cancer Research At MIT, Centre National de la Recherche Scientifique, Inserm, Institut Curie
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,043
Funders: Pharmaceutical Research and Manufacturers of America Foundation, Melanoma Research Alliance, Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, National Institutes of Health, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institute of Biomedical Imaging and Bioengineering
Awards: G1068653756, Controlled Release of Macromolecules, G2274913027, Dermatology Training Grant, A new high-throughput gastrointestinal tract explant platform for drug formulation discovery and metabolic disease modulation, G4357363684, G5797641063, G8008685062, G9000163483, MITF from control of pigmentation to melanoma risk, Predicting Transcriptional and Epigenetic Networks in Cancer from Sequencing Data
OpenAlex ID: W1552053194