Histone chaperone HIRA is required for melanocyte stem cell maintenance and suppression of hair graying during ageing

Farah Jaber-Hijazi, Jeff Pawlikowski, Claire Brock, Peter D. Adams*, Karthic Swaminathan, Laura M. Machesky

*Corresponding author for this work

Research output: Contribution to journalMeeting Abstractpeer-review

Abstract

Hair follicle pigmentation is due to a population of melanin producing cells, the melanocytes, which are maintained throughout the hair cycle via melanocyte stem cells (MSCs). Any defect in melanocyte function and/or maintenance or differentiation of MSCs can lead to pigment defects including premature hair graying, a hallmark of ageing. Here we describe a new conditional knockout mouse model (Tyr-Cre:Hirafl/fl) in which melanocytes are specifically deficient for Hira, a histone chaperone that deposits H3.3 histone variant in non-dividing cells at expressed genes and gene regulatory regions. Tyr::Cre HIRAfl/ fl mice are born with a mildly hypopigmented coat with a decrease in abundance of histone H3.3. Their coat colour becomes progressively white with age, a marked premature hair graying phenotype. While little effect is observed on melanocyte and MSC numbers in young Hira-deficient mice, aged mice are profoundly depleted of these cells suggesting a defect in stem cell maintenance. In addition, Hira-deficient
melanocytes fail to proliferate and survive in vitro. These data suggest an important role of HIRA in the maintenance of melanocyte stem cells and a healthy pigmentary system. More
generally, we anticipate that this model can inform on the role of proper epigenetic control and epigenetic maintenance in healthy aging.
Original languageEnglish
Pages (from-to)e65-e65
Number of pages1
JournalPigment Cell and Melanoma Research
Volume29
Issue number6
Early online date9 Sep 2016
DOIs
Publication statusPublished - 7 Feb 2017
Externally publishedYes
Event20th European Society for Pigment Cell Research Meeting - Campus, Via Adamello, Milan, Italy
Duration: 12 Sep 201615 Sep 2016
Conference number: 20

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