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

doi:10.1111/pcmr.12515

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 language	English
Pages (from-to)	e65-e65
Number of pages	1
Journal	Pigment Cell and Melanoma Research
Volume	29
Issue number	6
Early online date	9 Sept 2016
DOIs	https://doi.org/10.1111/pcmr.12515
Publication status	Published - 7 Feb 2017
Externally published	Yes
Event	20th European Society for Pigment Cell Research Meeting - Campus, Via Adamello, Milan, Italy Duration: 12 Sept 2016 → 15 Sept 2016 Conference number: 20

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@article{2a6c9d94240d478390ccabadff448caf,

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

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-deficientmelanocytes 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. Moregenerally, we anticipate that this model can inform on the role of proper epigenetic control and epigenetic maintenance in healthy aging.",

author = "Farah Jaber-Hijazi and Jeff Pawlikowski and Claire Brock and Adams, {Peter D.} and Karthic Swaminathan and Machesky, {Laura M.}",

year = "2017",

month = feb,

day = "7",

doi = "10.1111/pcmr.12515",

language = "English",

volume = "29",

pages = "e65--e65",

journal = "Pigment Cell and Melanoma Research",

issn = "1755-1471",

publisher = "John Wiley & Sons, Inc.",

number = "6",

note = "20th European Society for Pigment Cell Research Meeting, 20th ESPCR Meeting ; Conference date: 12-09-2016 Through 15-09-2016",

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TY - JOUR

T1 - Histone chaperone HIRA is required for melanocyte stem cell maintenance and suppression of hair graying during ageing

AU - Jaber-Hijazi, Farah

AU - Pawlikowski, Jeff

AU - Brock, Claire

AU - Adams, Peter D.

AU - Swaminathan, Karthic

AU - Machesky, Laura M.

N1 - Conference code: 20

PY - 2017/2/7

Y1 - 2017/2/7

N2 - 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-deficientmelanocytes 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. Moregenerally, we anticipate that this model can inform on the role of proper epigenetic control and epigenetic maintenance in healthy aging.

AB - 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-deficientmelanocytes 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. Moregenerally, we anticipate that this model can inform on the role of proper epigenetic control and epigenetic maintenance in healthy aging.

U2 - 10.1111/pcmr.12515

DO - 10.1111/pcmr.12515

M3 - Meeting Abstract

SN - 1755-1471

VL - 29

SP - e65-e65

JO - Pigment Cell and Melanoma Research

JF - Pigment Cell and Melanoma Research

IS - 6

T2 - 20th European Society for Pigment Cell Research Meeting

Y2 - 12 September 2016 through 15 September 2016

ER -

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

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