title: YY1 regulates melanocyte development and function by cooperating with MITF.
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.
authors.affiliation: Department of Dermatology, Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Juying
authors.initials: J
authors.lastname: Li
authors.forename: Jun S
authors.initials: JS
authors.lastname: Song
authors.forename: Robert J A
authors.initials: RJ
authors.lastname: Bell
authors.forename: Thanh-Nga T
authors.initials: TN
authors.lastname: Tran
authors.forename: Rizwan
authors.initials: R
authors.lastname: Haq
authors.forename: Huifei
authors.initials: H
authors.lastname: Liu
authors.forename: Kevin T
authors.initials: KT
authors.lastname: Love
authors.forename: Robert
authors.initials: R
authors.lastname: Langer
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Anderson
authors.forename: Lionel
authors.initials: L
authors.lastname: Larue
authors.forename: David E
authors.initials: DE
authors.lastname: Fisher
mesh_terms: D000818:Animals; D019070:Cell Lineage; D002470:Cell Survival; D004195:Disease Models, Animal; D018507:Gene Expression Regulation, Developmental; D006200:Hair Color / Q000235:genetics; D006801:Humans; D008544:Melanocytes / Q000166:cytology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics / Q000378:metabolism*; D010858:Pigmentation / Q000235:genetics; D014849:Waardenburg Syndrome / Q000235:genetics / Q000378:metabolism; D050986:YY1 Transcription Factor / Q000235:genetics* / Q000378:metabolism
chemical_list: D051739:Microphthalmia-Associated Transcription Factor; C497235:Mitf protein, mouse; D050986:YY1 Transcription Factor; C494699:Yy1 protein, mouse