A PRDM16-CtBP1/2 Complex Interacts with HDAC1/2 to Regulate Transcriptional Programs of Neurogenesis and Guide Cortical Neuron Migration DOI Creative Commons

Sophie Warren,

Bader El Farran,

Sungyun Kang

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 18, 2024

ABSTRACT Chromatin regulation of transcriptional enhancers plays a central role in cell fate specification and differentiation. However, how the coordinated activity transcription factors chromatin-modifying enzymes regulates neural stem cells (NSCs) dictates subsequent stages neuronal differentiation migration is not well understood. The histone methyltransferase PRDM16 expressed NSCs developing mouse human cerebral cortex essential for determining position upper-layer cortical neurons. Here, we report that interacts with C-terminal binding protein 1 (CtBP1) CtBP2 to control programs neurogenesis regulate neuron migration. CtBP1/2 co-regulate by interacting deacetylase (HDAC1) HDAC2, lysine-specific demethylase (LSD1). In addition, our results suggest CCCTC-binding factor CTCF key recruiting enhancers. These findings underscore reduced interactions between ubiquitous chromatin regulators may contribute neurodevelopmental deficits patients haploinsufficiency.

Language: Английский

Brain and cancer associated binding domain mutations provide insight into CTCF’s relationship with chromatin and its contribution to gene regulation DOI Open Access
Catherine Do,

Guimei Jiang,

Giulia Cova

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 12, 2024

Here we used a series of CTCF mutations to explore CTCF's relationship with chromatin and its contribution gene regulation. impact depends on the genomic context bound sites unique binding properties WT mutant proteins. Specifically, signal strength is linked changes in accessibility, ability block cohesin stability. Multivariate modelling reveals that both accessibility contribute independently insulation, however has stronger effect. have bidirectional such at sites, reduced cohesin-dependent, specific fashion. In addition, each alters TF an indirect manner, which impart most influence rewiring transcriptional networks cell's differentiate. Collectively, perturbations provide rich resource for determining site-specific effects.

Language: Английский

Citations

5
Binding domain mutations provide insight into CTCF’s relationship with chromatin and its contribution to gene regulation DOI Creative Commons
Catherine Do,

Guimei Jiang,

Giulia Cova

et al.

Cell Genomics, Journal Year: 2025, Volume and Issue: unknown, P. 100813 - 100813

Published: March 1, 2025

Here we used a series of CTCF mutations to explore CTCF's relationship with chromatin and its contribution gene regulation. impact depends on the genomic context bound sites unique binding properties WT mutant proteins. Specifically, signal strength is linked changes in accessibility, ability block cohesin stability. Multivariate modeling reveals that both accessibility contribute independently insulation, but has stronger effect. have bidirectional such at sites, reduced cohesin-dependent, mutant-specific fashion. In addition, each alters TF an indirect manner, which impart most influence rewiring transcriptional networks cell's differentiate. Collectively, perturbations provide rich resource for determining site-specific effects.

Language: Английский

Citations

0
Editorial overview: Emerging perspectives in genome architecture and gene regulation DOI
Marcelo Nöllmann, Anders S. Hansen

Current Opinion in Genetics & Development, Journal Year: 2025, Volume and Issue: 93, P. 102355 - 102355

Published: May 12, 2025

Language: Английский

Citations

0
A genome wide code to define cell-type specific CTCF binding and chromatin organization DOI Open Access
Catherine Do,

Guimei Jiang,

Paul Zappile

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 3, 2024

CTCF-mediated chromatin folding plays a key role in gene regulation, however the mechanisms underlying cell type-specific control are not fully elucidated. Comprehensive analyses reveal that CTCF binding stability and cohesin overlap mice humans is regulated by species specific differences accessibility, presence of extended Up Downstream site sequences motifs corresponding to expressed TFs enriched at most bound sites. repositions nucleosomes asymmetrically, with linker spacing altered while cohesin-mediated nucleosome phasing affected surrounding similarly impact insulation. Importantly, transcriptional programs determine motif enrichment sites, reflecting stabilizing/destabilizing effect individual TFs. These studies identify profiles, linked local long-range organization.

Language: Английский

Citations

2
Genetic factors mediating long-range enhancer–promoter communication in mammalian development DOI Creative Commons
Grace Bower, Evgeny Z. Kvon

Current Opinion in Genetics & Development, Journal Year: 2024, Volume and Issue: 90, P. 102282 - 102282

Published: Nov. 22, 2024

Language: Английский

Citations

1
A PRDM16-CtBP1/2 Complex Interacts with HDAC1/2 to Regulate Transcriptional Programs of Neurogenesis and Guide Cortical Neuron Migration DOI Creative Commons

Sophie Warren,

Bader El Farran,

Sungyun Kang

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 18, 2024

ABSTRACT Chromatin regulation of transcriptional enhancers plays a central role in cell fate specification and differentiation. However, how the coordinated activity transcription factors chromatin-modifying enzymes regulates neural stem cells (NSCs) dictates subsequent stages neuronal differentiation migration is not well understood. The histone methyltransferase PRDM16 expressed NSCs developing mouse human cerebral cortex essential for determining position upper-layer cortical neurons. Here, we report that interacts with C-terminal binding protein 1 (CtBP1) CtBP2 to control programs neurogenesis regulate neuron migration. CtBP1/2 co-regulate by interacting deacetylase (HDAC1) HDAC2, lysine-specific demethylase (LSD1). In addition, our results suggest CCCTC-binding factor CTCF key recruiting enhancers. These findings underscore reduced interactions between ubiquitous chromatin regulators may contribute neurodevelopmental deficits patients haploinsufficiency.

Language: Английский

Citations

0