Kdm1a safeguards the topological boundaries of PRC2-repressed genes and prevents aging-related euchromatinization in neurons

Beatriz del Blanco (), Sergio Niñerola, Ana M. Martín-González, Juan Paraíso-Luna, Minji Kim, Rafael Muñoz-Viana, Carina Racovac, Jose V. Sanchez-Mut, Yijun Ruan and Ángel Barco ()
Additional contact information
Beatriz del Blanco: Instituto de Neurociencias (Universidad Miguel Hernández - Consejo Superior de Investigaciones Científicas). Av. Santiago Ramón y Cajal s/n. Sant Joan d’Alacant
Sergio Niñerola: Instituto de Neurociencias (Universidad Miguel Hernández - Consejo Superior de Investigaciones Científicas). Av. Santiago Ramón y Cajal s/n. Sant Joan d’Alacant
Ana M. Martín-González: Instituto de Neurociencias (Universidad Miguel Hernández - Consejo Superior de Investigaciones Científicas). Av. Santiago Ramón y Cajal s/n. Sant Joan d’Alacant
Juan Paraíso-Luna: Instituto de Neurociencias (Universidad Miguel Hernández - Consejo Superior de Investigaciones Científicas). Av. Santiago Ramón y Cajal s/n. Sant Joan d’Alacant
Minji Kim: The Jackson laboratory for Genomic Medicine
Rafael Muñoz-Viana: Instituto de Neurociencias (Universidad Miguel Hernández - Consejo Superior de Investigaciones Científicas). Av. Santiago Ramón y Cajal s/n. Sant Joan d’Alacant
Carina Racovac: Instituto de Neurociencias (Universidad Miguel Hernández - Consejo Superior de Investigaciones Científicas). Av. Santiago Ramón y Cajal s/n. Sant Joan d’Alacant
Jose V. Sanchez-Mut: Instituto de Neurociencias (Universidad Miguel Hernández - Consejo Superior de Investigaciones Científicas). Av. Santiago Ramón y Cajal s/n. Sant Joan d’Alacant
Yijun Ruan: The Jackson laboratory for Genomic Medicine
Ángel Barco: Instituto de Neurociencias (Universidad Miguel Hernández - Consejo Superior de Investigaciones Científicas). Av. Santiago Ramón y Cajal s/n. Sant Joan d’Alacant

Nature Communications, 2024, vol. 15, issue 1, 1-20

Abstract: Abstract Kdm1a is a histone demethylase linked to intellectual disability with essential roles during gastrulation and the terminal differentiation of specialized cell types, including neurons, that remains highly expressed in the adult brain. To explore Kdm1a’s function in adult neurons, we develop inducible and forebrain-restricted Kdm1a knockouts. By applying multi-omic transcriptome, epigenome and chromatin conformation data, combined with super-resolution microscopy, we find that Kdm1a elimination causes the neuronal activation of nonneuronal genes that are silenced by the polycomb repressor complex and interspersed with active genes. Functional assays demonstrate that the N-terminus of Kdm1a contains an intrinsically disordered region that is essential to segregate Kdm1a-repressed genes from the neighboring active chromatin environment. Finally, we show that the segregation of Kdm1a-target genes is weakened in neurons during natural aging, underscoring the role of Kdm1a safeguarding neuronal genome organization and gene silencing throughout life.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-45773-3 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45773-3

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-45773-3

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().