pH-controlled histone acetylation amplifies melanocyte differentiation downstream of MITF.
epigenetics and zebrafish
histone acetylation
p300/CBP
pH regulation
pigmentation
Journal
EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049
Informations de publication
Date de publication:
07 01 2020
07 01 2020
Historique:
received:
22
04
2019
revised:
04
10
2019
accepted:
15
10
2019
pubmed:
12
11
2019
medline:
28
4
2021
entrez:
12
11
2019
Statut:
ppublish
Résumé
Tanning response and melanocyte differentiation are mediated by the central transcription factor MITF. This involves the rapid and selective induction of melanocyte maturation genes, while concomitantly the expression of other effector genes is maintained. In this study, using cell-based and zebrafish model systems, we report on a pH-mediated feed-forward mechanism of epigenetic regulation that enables selective amplification of the melanocyte maturation program. We demonstrate that MITF activation directly elevates the expression of the enzyme carbonic anhydrase 14 (CA14). Nuclear localization of CA14 leads to an increase of the intracellular pH, resulting in the activation of the histone acetyl transferase p300/CBP. In turn, enhanced H3K27 histone acetylation at selected differentiation genes facilitates their amplified expression via MITF. CRISPR-mediated targeted missense mutation of CA14 in zebrafish results in the formation of immature acidic melanocytes with decreased pigmentation, establishing a central role for this mechanism during melanocyte differentiation in vivo. Thus, we describe an epigenetic control system via pH modulation that reinforces cell fate determination by altering chromatin dynamics.
Identifiants
pubmed: 31709752
doi: 10.15252/embr.201948333
pmc: PMC6945066
doi:
Substances chimiques
Histones
0
Microphthalmia-Associated Transcription Factor
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e48333Subventions
Organisme : Council for scientific and Industrial Research (CSIR)
ID : BSC0302
Pays : International
Organisme : Council for scientific and Industrial Research (CSIR)
ID : MLP1810
Pays : International
Organisme : Council for scientific and Industrial Research (CSIR)
ID : OLP1118
Pays : International
Organisme : Department of Biotechnology, Ministry of Science and Technology (DBT)
ID : GAP0182
Pays : International
Informations de copyright
© 2019 The Authors.
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