MER57E3 transposable element subfamily co-opted for gene regulation in human early neural development DOI
Michelle A. Paz, Umut Yildiz, Minyoung Kim

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: April 7, 2025

Abstract Background Long dismissed as mere genomic parasites, transposable elements (TEs) are now recognized major drivers of genome evolution. TEs serve a source cell-type specific cis-regulatory elements, influencing gene expression and observable phenotypes. However, the precise TE regulatory roles in different contexts remain largely unexplored impact on transcriptional networks contribution to disease risk is likely deeply underestimated. Results Using multimapper-aware strategy, we systematically characterised epigenetic profile brain. This analysis revealed that MER57E3, primate-specific subfamily, exhibits strong enrichment for active, absence repressive, histone modifications across six brain cell types. MER57E3 copies predominantly located near zinc finger genes enriched homeodomain motifs by brain-specific transcription factors, including GBX1 BSX. Upon CRISPR interference (CRISPRi) targeting copies, RNA-seq demonstrated downregulation key neurogenesis-related PAX6 NEUROG2. Conclusions Our data indicate members subfamily regulate critical neurogenesis during neural progenitor (NPC) development. Moreover, this study emphasises importance characterising TEs, offering new insights into how their dysregulation may contribute pathogenesis neurodevelopmental disorders.

Language: Английский

Epigenome dynamics in early mammalian embryogenesis DOI

Adam Burton,

Maria‐Elena Torres‐Padilla

Nature Reviews Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: April 3, 2025

Language: Английский

Citations

0
MER57E3 transposable element subfamily co-opted for gene regulation in human early neural development DOI
Michelle A. Paz, Umut Yildiz, Minyoung Kim

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: April 7, 2025

Abstract Background Long dismissed as mere genomic parasites, transposable elements (TEs) are now recognized major drivers of genome evolution. TEs serve a source cell-type specific cis-regulatory elements, influencing gene expression and observable phenotypes. However, the precise TE regulatory roles in different contexts remain largely unexplored impact on transcriptional networks contribution to disease risk is likely deeply underestimated. Results Using multimapper-aware strategy, we systematically characterised epigenetic profile brain. This analysis revealed that MER57E3, primate-specific subfamily, exhibits strong enrichment for active, absence repressive, histone modifications across six brain cell types. MER57E3 copies predominantly located near zinc finger genes enriched homeodomain motifs by brain-specific transcription factors, including GBX1 BSX. Upon CRISPR interference (CRISPRi) targeting copies, RNA-seq demonstrated downregulation key neurogenesis-related PAX6 NEUROG2. Conclusions Our data indicate members subfamily regulate critical neurogenesis during neural progenitor (NPC) development. Moreover, this study emphasises importance characterising TEs, offering new insights into how their dysregulation may contribute pathogenesis neurodevelopmental disorders.

Language: Английский

Citations

0