PUBLICATION

A histone demethylase is necessary for regeneration in zebrafish

Authors

Stewart, S., Tsun, Z.Y., and Izpisúa Belmonte, J.C.

ID

ZDB-PUB-091120-38

Date

2009

Source

Proceedings of the National Academy of Sciences of the United States of America 106(47): 19889-19894 (Journal)

Registered Authors

Izpisúa Belmonte, Juan Carlos

Keywords

chromatin, polycomb

MeSH Terms

Jumonji Domain-Containing Histone Demethylases/genetics
Jumonji Domain-Containing Histone Demethylases/metabolism*
Histones/genetics
Histones/metabolism
Methylation
Oligonucleotides, Antisense/genetics
Oligonucleotides, Antisense/metabolism
Animals
Lysine/metabolism
Chromatin/metabolism
Zebrafish Proteins/genetics
Zebrafish Proteins/metabolism*
Humans
Zebrafish/anatomy & histology
Zebrafish/physiology*
Extremities/anatomy & histology
Extremities/physiology
Regeneration/physiology*
Promoter Regions, Genetic
Homeodomain Proteins/genetics
Homeodomain Proteins/metabolism

(all 21)

PubMed

19897725 Full text @ Proc. Natl. Acad. Sci. USA

Abstract

Urodele amphibians and teleost fish regenerate amputated body parts via a process called epimorphic regeneration. A hallmark of this phenomenon is the reactivation of silenced developmental regulatory genes that previously functioned during embryonic patterning. We demonstrate that histone modifications silence promoters of numerous genes involved in zebrafish caudal fin regeneration. Silenced developmental regulatory genes contain bivalent me(3)K4/me(3)K27 H3 histone modifications created by the concerted action of Polycomb (PcG) and Trithorax histone methyltransferases. During regeneration, this silent, bivalent chromatin is converted to an active state by loss of repressive me(3)K27 H3 modifications, occurring at numerous genes that appear to function during regeneration. Loss-of-function studies demonstrate a requirement for a me(3)K27 H3 demethylase during fin regeneration. These results indicate that histone modifications at discreet genomic positions may serve as a crucial regulatory event in the initiation of fin regeneration.

Genes / Markers

Figures

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Expression

Gene	Antibody	Fish	Conditions	Stage	Anatomy	Assay	Figure
kdm6a		WT	physical alteration: anatomical structure	Day 4	caudal fin apical epidermal cap	ISH	Fig. 3
kdm6a		WT	physical alteration: anatomical structure	Day 4	caudal fin regeneration epithelium	ISH	Fig. 3
kdm6al		WT	physical alteration: anatomical structure	Day 4	caudal fin regeneration epithelium	ISH	Fig. 3
kdm6ba		WT	physical alteration: anatomical structure	Day 4	caudal fin apical epidermal cap	ISH	Fig. 3
kdm6ba		WT	physical alteration: anatomical structure	Day 4	caudal fin regeneration epithelium	ISH	Fig. 3
kdm6bb		WT	physical alteration: anatomical structure	Day 4	caudal fin apical epidermal cap	ISH	Fig. 3
msx1b	ab1-msx	WT	physical alteration: anatomical structure	Day 4	caudal fin blastema	IHC	Fig. 3
tp63	ab1-tp63	WT	physical alteration: anatomical structure	Day 4	caudal fin regeneration epithelium	IHC	Fig. 3

1 - 8 of 8

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT + MO1-kdm6bb	physical alteration: anatomical structure	Day 4	caudal fin blastema decreased size, abnormal	Fig. 4
WT + MO1-kdm6bb	physical alteration: anatomical structure	Day 4	caudal fin blastema decreased size, abnormal	Fig. 5
WT + MO1-kdm6bb	physical alteration: anatomical structure	Day 4	fin regeneration disrupted, abnormal	Fig. 4
WT + MO1-kdm6bb	physical alteration: anatomical structure	Day 4	fin regeneration disrupted, abnormal	Fig. 5
WT + MO2-kdm6bb	physical alteration: anatomical structure	Day 4	caudal fin blastema decreased size, abnormal	Fig. 4
WT + MO2-kdm6bb	physical alteration: anatomical structure	Day 4	caudal fin blastema decreased size, abnormal	Fig. 5
WT + MO2-kdm6bb	physical alteration: anatomical structure	Day 4	fin regeneration disrupted, abnormal	Fig. 4
WT + MO2-kdm6bb	physical alteration: anatomical structure	Day 4	fin regeneration disrupted, abnormal	Fig. 5

1 - 8 of 8

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Mutations / Transgenics

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
kdm6bb	MO2-kdm6bb	MRPHLNO
kdm6bb	MO1-kdm6bb	MRPHLNO

Fish

Fish
WT
WT + MO1-kdm6bb
WT + MO2-kdm6bb

Antibodies

Name	Type	Antigen Genes	Isotypes	Host Organism
Ab1-msx	monoclonal	msx1b	IgG1	Mouse
Ab1-tp63	monoclonal	tp63	IgG2a	Mouse
Ab8-h3	polyclonal		IgG	Rabbit

Orthology

Gene	Orthology
kdm6a

Engineered Foreign Genes

Mapping

Stewart et al., 2009 ZDB-PUB-091120-38 PMID:19897725

A histone demethylase is necessary for regeneration in zebrafish

Stewart et al., 2009

ZDB-PUB-091120-38
PMID:19897725