Genomics

Dataset Information

238

Epigenetic regulation of Atrophin1 by lysine-specific demethylase 1 is required for cortical progenitor maintenance


ABSTRACT: Lysine-specific demethylase 1 (LSD1) is involved in gene regulation and development; however, its precise function, molecular targets and underlying mechanisms during development are poorly understood. Here, we show that LSD1 is required for neuronal progenitor cell (NPC) maintenance during cortical development. A ChIP-seq analysis identified a LSD1 binding site (LBAL) downstream of Atrophin1 (ATN1). Surprisingly, tranylcypromine (LSD1 inhibitor) treatment increased H3K4 methylation at LBAL, leading to ATN1 repression and NPC differentiation. Knockdown of LSD1 and ATN1 phenocopied each other in inducing NPC premature differentiation and depletion which could be rescued by ATN1 overexpression, suggesting that LSD1 controls NPC differentiation via regulation of ATN1 methylation status and expression. The involvement of LSD1 in ATN1 expression and NPC maintenance were confirmed in knockout mice. These findings hint at the potential application for the clinical drug, tranylcypromine, in the prevention and/or treatment of ATN1-associated degenerative disease, dentatorubral-pallidoluysian atrophy. Examination of LSD1 binding sites in neuronal progenitor cells.

ORGANISM(S): Rattus norvegicus  

SUBMITTER: Feng Zhang   Zhiheng Xu 

PROVIDER: E-GEOD-62770 | ArrayExpress | 2015-04-29

SECONDARY ACCESSION(S): SRP049334GSE62770PRJNA265087

REPOSITORIES: GEO, ArrayExpress, ENA

Similar Datasets

2013-06-25 | E-GEOD-40440 | ArrayExpress
2020-06-04 | PXD016080 | Pride
2012-04-05 | GSE18598 | GEO
| GSE86524 | GEO
2012-04-04 | E-GEOD-18598 | ArrayExpress
2012-01-03 | E-GEOD-27841 | ArrayExpress
2012-03-28 | E-GEOD-36346 | ArrayExpress
2014-02-15 | E-GEOD-54376 | ArrayExpress
2012-10-03 | E-GEOD-18515 | ArrayExpress
| GSE75719 | GEO