Gene of the Month – February: KDM5C

KDM5C plays a pivotal role in the complex process of neuron formation. A study published in Nature now shows that KDM5C acts in a specific developmental window directly on WNT signaling and thus ensures timely differentiation of neuronal progenitor cells. Variants in KDM5C are known to cause neurodevelopmental disorders with intellectual disability, but the underlying mechanisms have not yet been revealed.

The protein encoded by KDM5C is a histone demethylase that regulates gene expression by altering chromatin conformation. The authors of the study used patient-derived cells and a knockout mouse model to investigate cellular processes, gene expression, chromatin and mice behavior affected by KDM5C variants. The results suggest that KDM5C directly regulates expression of specific target genes involved in WNT signaling and thus ensures differentiation of primary into intermediary progenitor cells during neurogenesis. The researchers also revealed that transient modulation of WNT signaling is sufficient to reverse gene expression and chromatin-related alterations in patient-derived cells and to induce them in wildtype cells. This might form the basis for a potential novel therapeutic target in the future.

Karwacki-Neisius V, Jang A, Cukuroglu E, … Shi Y. WNT signalling control by KDM5C during development affects cognition. Nature. 2024 Feb 21. doi: 10.1038/s41586-024-07067-y. Epub ahead of print.

Article in PubMed

Gene of the Month – February: KDM5C

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