Our results indicate that oxidation of TAF10 by LOXL2 induces its release from its promoters, leading to a block in TFIID-dependent gene transcription. Since TFIID complex is crucial for the expression of Nanog, Klf4, Sox2 and Oct4 and for maintaining the pluripotent state of embryonic stem cells, TAF10 oxidation by LOXL2 leads to inactivation of the pluripotency genes and a loss of pluripotent capacity in embryonic stem cells. Moreover, in vivo results demonstrate an essential role of LOXL2 in neural differentiation during zebrafish development: in the absence of LOXL2 the neural progenitor gene Sox2 is aberrantly overexpressed and neural differentiation is impaired.
LOXL2 Oxidizes Methylated TAF10 and Controls TFIID-Dependent Genes during Neural Progenitor Differentiation.
Specimen part
View SamplesAlthough heterochromatin is enriched with repressive traits, it is also actively transcribed, giving rise to large amounts of non-coding RNAs. Although these RNAs are responsible for the formation and maintenance of heterochromatin, little is known about how their transcription is regulated. Here we show that the Snail1 transcription factor represses pericentromeric transcription, acting through the H3K4 deaminase LOXL2. Since Snail1 plays a key role in the epithelial to mesenchymal transition (EMT), we analyzed the regulation of mouse heterochromatin transcription in this process. At the onset of EMT, one of the major structural heterochromatin proteins, HP1a, is transiently released from heterochromatin foci in a Snail1/LOXL2dependent manner during EMT, concomitantly with a down-regulation of major satellite transcription. Global transcriptome analysis indicated that ectopic expression of heterochromatin transcripts affects the transcription profile of EMT-related genes. Additionally, preventing the down-regulation of major satellite transcripts compromised the migratory and invasive behavior of mesenchymal cells. We propose that Snail1 regulates heterochromatin transcription through the histone-modifying enzyme, LOXL2, thus creating the favorable transcriptional state necessary for completing EMT.
Regulation of heterochromatin transcription by Snail1/LOXL2 during epithelial-to-mesenchymal transition.
Cell line, Treatment
View SamplesGene expression from MDA-MB-231 cells shControl and shLOXL2.
Lysyl oxidase-like 2 (LOXL2) oxidizes trimethylated lysine 4 in histone H3.
Cell line
View SamplesA genome-wide RNA expression study based on a Phase II randomized placebo-controlled clinical trial of topiramate (TPM) treatment of methamphetamine (METH) dependence.
Transcriptome profiling and pathway analysis of genes expressed differentially in participants with or without a positive response to topiramate treatment for methamphetamine addiction.
Sex, Age, Specimen part, Treatment, Race, Subject, Time
View Samples