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

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 con...

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Bibliographic Details
Published in:Molecular cell 2015-06, Vol.58 (5), p.755-766
Main Authors: Iturbide, Ane, Pascual-Reguant, Laura, Fargas, Laura, Cebrià, Joan Pau, Alsina, Berta, García de Herreros, Antonio, Peiró, Sandra
Format: Article
Language:English
Subjects:
Amino Acid Oxidoreductases - physiology
Animals
Cell Differentiation
Epigenesis, Genetic
Gens
HEK293 Cells
Humans
Methylation
Neural Stem Cells - physiology
Oxidation-Reduction
Protein Processing, Post-Translational
Proteïnes
TATA-Binding Protein Associated Factors - metabolism
Transcription Factor TFIID - metabolism
Transcription Factor TFIID - physiology
Zebrafish
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Summary: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. [Display omitted] •LOXL2 oxidizes methylated TAF10•LOXL2 represses TFIID transcription-dependent genes•LOXL2 is key in the balance between pluripotency and differentiation in ESCs Iturbide et al. show that lysine oxidation of methylated TAF10 contained in a TFIID complex inhibits the ability of TFIID to activate transcription. This findings highlight oxidation as a controlled protein modification with a critical role in pluripotency gene transcription.
ISSN:1097-2765
1097-4164
DOI:10.1016/j.molcel.2015.04.012