Dataset Information

MBD2 modulates heterochromatin architecture and composition

ABSTRACT: Heterochromatin (HC) is essential for nuclear integrity, genome stability, and gene regulation with pericentric heterochromatin (PCH) playing a key role. However, the mechanisms governing PCH compartmentalization remain poorly understood. Recent studies suggest that phase separation (PS) underlies the organization of various subnuclear compartments, including PCH. In this study, we integrated spatial proteomics, in vitro phase separation assays, and advanced PS prediction tools to identify and characterize candidate PS scaffold proteins involved in HC compartmentalization, particularly in PCH. We found that HC forms dynamic, phase-separated condensates that selectively enrich specific proteins. Approximately 1,000 HC PS-associated proteins were predicted, with around 250 predicted to possess scaffold PS properties. Further subcellular analysis identified 20 potential PS scaffold proteins in PCH, including Methyl-CpG binding domain protein 2 (MBD2). MBD2, a member of the NuRD complex, was shown to undergo LLPS via coiled-coil-mediated homooligomerization, forming liquid-like condensates that likely regulate PCH organization, as well as MBD-mC-mediated PPPS. This study advances our understanding of PCH compartmentalization by highlighting the role of MBD2 in PCH dynamics and provides new insights into the molecular mechanisms underlying nuclear architecture and opens avenues for future research into genome regulation and stability.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: M. Cristina Cardoso

LAB HEAD: M Cristina Cardoso

PROVIDER: PXD055626 | Pride | 2025-12-29

REPOSITORIES: Pride

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			Action	DRS
	20231025_EXPL0_EnUg_SA_U330_44min_DIA_3_H_1.raw	Raw
	20231025_EXPL0_EnUg_SA_U330_44min_DIA_3_H_10.raw	Raw
	20231025_EXPL0_EnUg_SA_U330_44min_DIA_3_H_11.raw	Raw
	20231025_EXPL0_EnUg_SA_U330_44min_DIA_3_H_12.raw	Raw
	20231025_EXPL0_EnUg_SA_U330_44min_DIA_3_H_13.raw	Raw

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Heterochromatome wide analyses reveal MBD2 as a phase separation scaffold for heterochromatin compartmentalization and composition.

Zhang Hui H Ugur Enes E Hake Christian C Romero Hector H Arroyo Maria M Mahmoud Marah M Lermyte Frederik F Leonhardt Heinrich H Cardoso M Cristina MC

Nucleic acids research 20251101 22

Heterochromatin is essential for nuclear integrity, genome stability, and gene regulation. However, the mechanisms governing heterochromatin compartmentalization remain poorly understood. Recent studies suggest that phase separation underlies the organization of heterochromatin. Here, we integrated quantitative spatial proteomics, phase separation assays, and phase separation prediction tools to identify and characterize candidate phase separation scaffold proteins involved in heterochromatin co ...[more]

PMID: 41416523

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