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CARM1 hypermethylates the NuRD chromatin remodeling complex to promote cell cycle gene expression and breast cancer development [ChIP-Seq]

ABSTRACT: CARM1 hypermethylates the NuRD chromatin remodeling complex to promote cell cycle gene expression and breast cancer development [ChIP-Seq]

PROVIDER: PRJNA1089933 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28394659_1.fastq.gz	Fastqsanger.gz
	SRR28394659_2.fastq.gz	Fastqsanger.gz
	SRR28394660_1.fastq.gz	Fastqsanger.gz
	SRR28394660_2.fastq.gz	Fastqsanger.gz

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CARM1 interacts and hypermethylates the NuRD chromatin remodeling complex to promote gene transcriptional activation and cell cycle progression

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 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.

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CARM1 interacts and hypermethylates the NuRD chromatin remodeling complex to promote gene transcriptional activation and cell cycle progression

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CARM1 hypermethylates the NuRD chromatin remodeling complex to promote cell cycle gene expression and breast cancer development [ChIP-Seq]

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 NuRD are associated with active genes and modulates their expression, but the underlying molecular mechanisms remain ill-defined. Here, we reported that the transcriptional coactivator CARM1 is associated with NuRD through its direct interaction with the GATAD2A/2B subunit, expanding the activities of NuRD to include protein arginine methylation. CARM1 and NuRD co-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 a key subunit in the NuRD complex, GATAD2A/2B, which is critical for the recruitment of the NuRD complex. The biological 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 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.

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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.

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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.

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