PUBLICATION

LOXL2 Oxidizes Methylated TAF10 and Controls TFIID-Dependent Genes during Neural Progenitor Differentiation

Authors

Iturbide, A., Pascual-Reguant, L., Fargas, L., Cebrià, J.P., Alsina, B., García de Herreros, A., Peiró, S.

ID

ZDB-PUB-150512-8

Date

2015

Source

Molecular Cell 58(5): 755-66 (Journal)

Registered Authors

Alsina, Berta

Keywords

none

MeSH Terms

Amino Acid Oxidoreductases/physiology*
Protein Processing, Post-Translational*
Animals
Zebrafish
Oxidation-Reduction
Humans
TATA-Binding Protein Associated Factors/metabolism*
Epigenesis, Genetic
Methylation
Cell Differentiation*
HEK293 Cells
Transcription Factor TFIID/metabolism
Transcription Factor TFIID/physiology*
Neural Stem Cells/physiology*

(all 14)

PubMed

25959397 Full text @ Mol. Cell

Abstract

Protein function is often regulated and controlled by posttranslational modifications, such as oxidation. Although oxidation has been mainly considered to be uncontrolled and nonenzymatic, many enzymatic oxidations occur on enzyme-selected lysine residues; for instance, LOXL2 oxidizes lysines by converting the ε-amino groups into aldehyde groups. Using an unbiased proteomic approach, we have identified methylated TAF10, a member of the TFIID complex, as a LOXL2 substrate. LOXL2 oxidation of TAF10 induces its release from its promoters, leading to a block in TFIID-dependent gene transcription. In embryonic stem cells, this results in the inactivation of the pluripotency genes and loss of the pluripotent capacity. During zebrafish development, the absence of LOXL2 resulted in the aberrant overexpression of the neural progenitor gene Sox2 and impaired neural differentiation. Thus, lysine oxidation of the transcription factor TAF10 is a controlled protein modification and demonstrates a role for protein oxidation in regulating pluripotency genes.

Genes / Markers

Figures

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Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
loxl2a	AB	standard conditions	Prim-5	eye	ISH	Fig. S6
loxl2a	AB	standard conditions	Prim-5	midbrain	ISH	Fig. S6
loxl2a	AB	standard conditions	Prim-5	midbrain hindbrain boundary	ISH	Fig. S6
loxl2a	AB	standard conditions	Prim-5	whole organism	ISH	Fig. S6
loxl2b	AB	standard conditions	Prim-5	whole organism	ISH	Fig. S6
neurod1	AB	control	Prim-5	central nervous system	ISH	Fig. 7
neurod1	AB	control	Prim-5	eye	ISH	Fig. 7
neurod1	AB	control	Prim-5	hindbrain	ISH	Fig. 7
neurod1	AB	control	Prim-5	spinal cord	ISH	Fig. 7
neurod1	AB + MO1-loxl2b + MO3-loxl2a	standard conditions	Prim-5	central nervous system	ISH	Fig. 7

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
AB + MO1-loxl2b + MO3-loxl2a	standard conditions	Prim-5	brain anterior region increased curvature, abnormal	Fig. 7
AB + MO1-loxl2b + MO3-loxl2a	standard conditions	Prim-5	brain morphology, abnormal	Fig. 7
AB + MO1-loxl2b + MO3-loxl2a	standard conditions	Prim-5	central nervous system neurod1 expression decreased distribution, abnormal	Fig. 7
AB + MO1-loxl2b + MO3-loxl2a	standard conditions	Prim-5	central nervous system sox2 expression increased distribution, abnormal	Fig. 7
AB + MO1-loxl2b + MO3-loxl2a	standard conditions	Prim-5	eye neurod1 expression decreased distribution, abnormal	Fig. 7
AB + MO1-loxl2b + MO3-loxl2a	standard conditions	Prim-5	eye sox2 expression increased distribution, abnormal	Fig. 7
AB + MO1-loxl2b + MO3-loxl2a	standard conditions	Prim-5	eye flattened, abnormal	Fig. 7
AB + MO1-loxl2b + MO3-loxl2a	standard conditions	Prim-5	hindbrain neurod1 expression decreased distribution, abnormal	Fig. 7
AB + MO1-loxl2b + MO3-loxl2a	standard conditions	Prim-5	hindbrain sox2 expression increased distribution, abnormal	Fig. 7
AB + MO1-loxl2b + MO3-loxl2a	standard conditions	Prim-5	spinal cord neurod1 expression decreased distribution, abnormal	Fig. 7

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Mutations / Transgenics

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
loxl2a	MO3-loxl2a	MRPHLNO
loxl2b	MO1-loxl2b	MRPHLNO

Fish

Fish
AB
AB + MO1-loxl2b + MO3-loxl2a

Antibodies

Orthology

Engineered Foreign Genes

Mapping

Iturbide et al., 2015 ZDB-PUB-150512-8 PMID:25959397

LOXL2 Oxidizes Methylated TAF10 and Controls TFIID-Dependent Genes during Neural Progenitor Differentiation

Iturbide et al., 2015

ZDB-PUB-150512-8
PMID:25959397