GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.
PMID:29370269
| Citation |
Patel, D, Shimomura, A, Majumdar, S, Holley, MC and Hashino, E (2018) The histone demethylase LSD1 regulates inner ear progenitor differentiation through interactions with Pax2 and the NuRD repressor complex. PLoS ONE 13:e0191689 |
|---|---|
| Abstract |
The histone demethylase LSD1 plays a pivotal role in cellular differentiation, particularly in silencing lineage-specific genes. However, little is known about how LSD1 regulates neurosensory differentiation in the inner ear. Here we show that LSD1 interacts directly with the transcription factor Pax2 to form the NuRD co-repressor complex at the Pax2 target gene loci in a mouse otic neuronal progenitor cell line (VOT-N33). VOT-N33 cells expressing a Pax2-response element reporter were GFP-negative when untreated, but became GFP positive after forced differentiation or treatment with a potent LSD inhibitor. Pharmacological inhibition of LSD1 activity resulted in the enrichment of mono- and di-methylation of H3K4, upregulation of sensory neuronal genes and an increase in the number of sensory neurons in mouse inner ear organoids. Together, these results identify the LSD1/NuRD complex as a previously unrecognized modulator for Pax2-mediated neuronal differentiation in the inner ear. |
| Links |
PubMed PMC5784988 Online version:10.1371/journal.pone.0191689 |
| Keywords |
|
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
| GO:0034648: histone demethylase activity (H3-dimethyl-K4 specific) |
ECO:0000315: |
F |
Figure 5B shows that the inhibition of LSD1 (alpha-LSD1), had significantly higher levels of H3K4me2 (di-methylation) versus the functioning LSD1 denoted as KDM1A in UNIPROT, in mice. |
complete | ||||
| GO:0034649: histone demethylase activity (H3-monomethyl-K4 specific) |
ECO:0000315: |
F |
Figure 5B shows that the inhibition of LSD1 (alpha-LSD1), had significantly higher levels of H3K4me1 (mono-methylation) versus the functioning LSD1, denoted as KDM1A in UNIPROT, in mice. |
complete | ||||
|
Colocalizes with |
GO:0016581: NuRD complex |
ECO:0000314: |
C |
Figure 2D shows how KDMA1 (called LSD1 in paper) is associated with the NuRD complex in mice. |
complete | |||
| GO:0045665: negative regulation of neuron differentiation |
ECO:0000316: |
UniProtKB:PAX2_MOUSE
|
P |
Figure 6 shows that PAX2 interacting with KDM1A (called LSD1 in paper) causes negitive regulation of neuronal differentiation in mice. |
complete | |||
|
Colocalizes with |
GO:0016581: NuRD complex |
ECO:0000314: |
C |
Figure 2C shows that PAX2 (Pax2 in paper) associates with the NuRD complex in mice. |
complete | |||
Notes
See also
References
See Help:References for how to manage references in GONUTS.
