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CARM1 is an integral component of the NuRD chromatin remodeling complex

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE131865 | GEO | 2025/05/19

REPOSITORIES: GEO

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CARM1 is an integral component of the NuRD chromatin remodeling complex

Project description:The nucleosome remodeling and deacetylase (NuRD) complex is a large multi-subunit complex that couples ATP-dependent chromatin-remodeling and histone deacetylase activities. Emerging evidence suggested that the NuRD complex is prevalently associated with gene transcriptional activation, but little is known about the underlying molecular mechanisms. Here, we reported that the transcriptional coactivator CARM1 is an integral component of the NuRD complex, expanding the activities of the NuRD complex to include arginine methylation. CARM1-associated NuRD binds and activates a large cohort of genes, including those implicated in cell cycle control, to facilitate the G1/S transition. This gene activation process requires CARM1 to catalyze methylation of histone 3 and a key subunit of the NuRD complex, GATAD2A/2B. The biological significance of this gene activation mechanism is underscored by the coordinated expression of both CARM1 and NuRD in breast cancers, which proves to be critical for breast cancer cell growth in vitro and tumorigenesis in vivo. These findings reveal a gene activation program that requires the dual specificity established by CARM1 on chromatin and a key chromatin remodeler.

2025-05-19 | GSE131863 | GEO

CARM1 is an integral component of the NuRD chromatin remodeling complex (RNA-Seq)

2025-05-19 | GSE131864 | GEO

CARM1 is an integral component of the NuRD chromatin remodeling complex

Project description:CARM1 is an integral component of the NuRD chromatin remodeling complex

| PRJNA545138 | ENA

CARM1 is an integral component of the NuRD chromatin remodeling complex

Project description:CARM1 is an integral component of the NuRD chromatin remodeling complex

| PRJNA545133 | ENA

CARM1 is an integral component of the NuRD chromatin remodeling complex (RNA-Seq)

Project description:CARM1 is an integral component of the NuRD chromatin remodeling complex (RNA-Seq)

| PRJNA545142 | ENA

CARM1 hypermethylates the NuRD chromatin remodeling complex to promote cell cycle gene expression and breast cancer development.

Project description:Protein arginine methyltransferase CARM1 has been shown to methylate a large number of non-histone proteins, and play important roles in gene transcriptional activation, cell cycle progress, and tumorigenesis. However, the critical substrates through which CARM1 exerts its functions remain to be fully characterized. Here, we reported that CARM1 directly interacts with the GATAD2A/2B subunit in the nucleosome remodeling and deacetylase (NuRD) complex, expanding the activities of NuRD to include protein arginine methylation. CARM1 and NuRD bind and activate a large cohort of genes with implications in cell cycle control to facilitate the G1 to S phase transition. This gene activation process requires CARM1 to hypermethylate GATAD2A/2B at a cluster of arginines, which is critical for the recruitment of the NuRD complex. The clinical significance of this gene activation mechanism is underscored by the high expression of CARM1 and NuRD in breast cancers, and the fact that knockdown CARM1 and NuRD inhibits cancer cell growth in vitro and tumorigenesis in vivo. Targeting CARM1-mediated GATAD2A/2B methylation with CARM1 specific inhibitors potently inhibit breast cancer cell growth in vitro and tumorigenesis in vivo. These findings reveal a gene activation program that requires arginine methylation established by CARM1 on a key chromatin remodeler, and targeting such methylation might represent a promising therapeutic avenue in the clinic.

| S-EPMC11229315 | biostudies-literature

SUMO is an Integral and Instructive Component of Chromatin in Cell Growth and Senescence

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-07-24 | E-GEOD-42213 | biostudies-arrayexpress

Suppression of SWI/SNF component Arid1a promotes mammalian regeneration through chromatin remodeling

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2016-03-30 | E-GEOD-76935 | biostudies-arrayexpress

SUMO is an Integral and Instructive Component of Chromatin in Cell Growth and Senescence

Project description:This SuperSeries is composed of the SubSeries listed below.

2013-07-24 | GSE42213 | GEO

The nucleosome remodeling and deacetylase chromatin remodeling (NuRD) complex is required for peripheral nerve myelination.

Project description:Several key transcription factors and coregulators important to peripheral nerve myelination have been identified, but the contributions of specific chromatin remodeling complexes to peripheral nerve myelination have not been analyzed. Chromodomain helicase DNA-binding protein 4 (Chd4) is the core catalytic subunit of the nucleosome remodeling and deacetylase (NuRD) chromatin remodeling complex. Previous studies have shown Chd4 interacts with Nab (NGFI-A/Egr-binding) corepressors, which are required for early growth response 2 (Egr2/Krox20), to direct peripheral nerve myelination by Schwann cells. In this study, we examined the developmental importance of the NuRD complex in peripheral nerve myelination through the generation of conditional Chd4 knock-out mice in Schwann cells (Chd4(loxP/loxP); P0-cre). Chd4 conditional null mice were found to have delayed myelination, radial sorting defects, hypomyelination, and the persistence of promyelinating Schwann cells. Loss of Chd4 leads to elevated expression of immature Schwann cell genes (Id2, c-Jun, and p75), and sustained expression of the promyelinating Schwann cell gene, Oct6/Scip, without affecting the levels of Egr2/Krox20. Furthermore, Schwann cell proliferation is upregulated in Chd4-null sciatic nerve. In vivo chromatin immunoprecipitation studies reveal recruitment of Chd4 and another NuRD component, Mta2, to genes that are positively and negatively regulated by Egr2 during myelination. Together, these results underscore the necessity of Chd4 function to guide proper terminal differentiation of Schwann cells and implicate the NuRD chromatin remodeling complex as a requisite factor in timely and stable peripheral nerve myelination.

| S-EPMC3292862 | biostudies-literature

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