The kinase NEK6 positively regulates LSD1 activity and accumulation in local chromatin sub-compartments DOI Creative Commons
Franziska Knodel,

Jürgen Eirich,

Sabine Pinter

et al.

Communications Biology, Journal Year: 2024, Volume and Issue: 7(1)

Published: Nov. 10, 2024

LSD1 plays a crucial role in mammalian biology, regulated through interactions with coregulators and post-translational modifications. Here we show that the kinase NEK6 stimulates activity cells observe strong colocalization of at distinct chromatin sub-compartments (CSCs). We demonstrate is substrate for phosphorylation N-terminal intrinsically disordered region (IDR) LSD1, which shows phase separation behavior vitro cells. The LSD1-IDR important functions to co-compartmentalize NEK6, histone peptides DNA. subsequent by supports concentration these CSCs, imperative dynamic control transcription. This suggest regulatory function our findings highlight modulating separation, expanding understanding regulation its implications cellular processes.

Language: Английский

Exploring protein-mediated compaction of DNA by coarse-grained simulations and unsupervised learning DOI
Marjolein de Jager,

Pauline J. Kolbeck,

Willem Vanderlinden

et al.

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

Published: March 30, 2024

ABSTRACT Protein-DNA interactions and protein-mediated DNA compaction play key roles in a range of biological processes. The length scales typically involved bending, bridging, looping, (≥1 kbp) are challenging to address experimentally or by all-atom molecular dynamics simulations, making coarse-grained simulations natural approach. Here we present simple generic model for the DNA-protein protein-protein interactions, investigate role latter protein-induced DNA. Our approach models as discrete worm-like chain. proteins treated grand-canonical ensemble protein-DNA binding strength is taken from experimental measurements. modeled an isotropic potential with imposed valency, without specific assumptions about geometry. To systematically quantitatively classify complexes, unsupervised machine learning pipeline that receives large set structural order parameters input, reduces dimensionality via principal component analysis, groups results using Gaussian mixture model. We apply our method recent data on viral genome-length HIV integrase find critical formation looped intermediate structures seen experimentally. methodology broadly applicable DNA-binding provides systematic quantitative analyzing their mesoscale complexes. SIGNIFICANCE central storage transmission genetic information frequently compacted condensed proteins. Their size dynamic nature make resulting complexes difficult probe simulations. explore ∼kbp interacting defined valency concentration. analysis uses define conformational states pathways between them. integrase. account observed intermediates simulated good agreement observations.

Language: Английский

Citations

3
Exploring protein-mediated compaction of DNA by coarse-grained simulations and unsupervised learning DOI
Marjolein de Jager,

Pauline J. Kolbeck,

Willem Vanderlinden

et al.

Biophysical Journal, Journal Year: 2024, Volume and Issue: 123(18), P. 3231 - 3241

Published: July 23, 2024

Language: Английский

Citations

1
The kinase NEK6 positively regulates LSD1 activity and accumulation in local chromatin sub-compartments DOI Creative Commons
Franziska Knodel,

Jürgen Eirich,

Sabine Pinter

et al.

Communications Biology, Journal Year: 2024, Volume and Issue: 7(1)

Published: Nov. 10, 2024

LSD1 plays a crucial role in mammalian biology, regulated through interactions with coregulators and post-translational modifications. Here we show that the kinase NEK6 stimulates activity cells observe strong colocalization of at distinct chromatin sub-compartments (CSCs). We demonstrate is substrate for phosphorylation N-terminal intrinsically disordered region (IDR) LSD1, which shows phase separation behavior vitro cells. The LSD1-IDR important functions to co-compartmentalize NEK6, histone peptides DNA. subsequent by supports concentration these CSCs, imperative dynamic control transcription. This suggest regulatory function our findings highlight modulating separation, expanding understanding regulation its implications cellular processes.

Language: Английский

Citations

0