Dual role of the arginine methyltransferase CARM1 in the regulation of c‐Fos target genes

Fauquier, Lucas; Duboé, Carine; Joré, Cécile; Trouche, Didier; Vandel, Laurence

doi:10.1096/fj.07-104604

Cited by 21 publications

(17 citation statements)

References 52 publications

(81 reference statements)

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“…Immunoprecipitation, Western blotting, RT-PCR, siRNA, and shRNA tranfections Immunoprecipitation and co-IP experiments were performed as described (Fauquier et al 2008). For RT-PCR, total RNA was extracted from cells using GenElute RNA extraction kit (Sigma).…”

Section: Plasmids and Recombinant Proteinsmentioning

confidence: 99%

Methylation specifies distinct estrogen-induced binding site repertoires of CBP to chromatin

Ceschin¹,

Walia²,

Wenk³

et al. 2011

Genes Dev.

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Multiple signaling pathways ultimately modulate the epigenetic information embedded in the chromatin of gene promoters by recruiting epigenetic enzymes. We found that, in estrogen-regulated gene programming, the acetyltransferase CREB-binding protein (CBP) is specifically and exclusively methylated by the coactivatorassociated arginine methyltransferase (CARM1) in vivo. CARM1-dependent CBP methylation and p160 coactivators were required for estrogen-induced recruitment to chromatin targets. Notably, methylation increased the histone acetyltransferase (HAT) activity of CBP and stimulated its autoacetylation. Comparative genome-wide chromatin immunoprecipitation sequencing (ChIP-seq) studies revealed a variety of patterns by which p160, CBP, and methyl-CBP (meCBP) are recruited (or not) by estrogen to chromatin targets. Moreover, significant target gene-specific variation in the recruitment of (1) the p160 RAC3 protein, (2) the fraction of a given meCBP species within the total CBP, and (3) the relative recruitment of different meCBP species suggests the existence of a target gene-specific ''fingerprint'' for coregulator recruitment. Crossing ChIP-seq and transcriptomics profiles revealed the existence of meCBP ''hubs'' within the network of estrogen-regulated genes. Together, our data provide evidence for an unprecedented mechanism by which CARM1-dependent CBP methylation results in geneselective association of estrogen-recruited meCBP species with different HAT activities and specifies distinct target gene hubs, thus diversifying estrogen receptor programming.

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Section: Plasmids and Recombinant Proteinsmentioning

confidence: 99%

Methylation specifies distinct estrogen-induced binding site repertoires of CBP to chromatin

Ceschin¹,

Walia²,

Wenk³

et al. 2011

Genes Dev.

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“…Methylation of these proteins increases steroid receptor transcription (Bauer et al, 2002;Chevillard-Briet et al, 2002;Daujat et al, 2002;Feng et al, 2006;Ma et al, 2001;Schurter et al, 2001;Xu et al, 2001). CARM1 also increases the transcriptional activity of other factors, including cFOS, p53 (TRP53), NFB and LEF1/TCF4 Covic et al, 2005;Fauquier et al, 2008;Koh et al, 2002;Miao et al, 2006;Teyssier et al, 2006;Yang et al, 2006). Furthermore, CARM1 methylates the RNA-binding proteins HuR and HuD (ELAVL1 and ELAVL4), modulating their ability to bind and stabilize transcripts (Fujiwara et al, 2006;Li et al, 2002;Yamaguchi et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

CARM1 is required for proper control of proliferation and differentiation of pulmonary epithelial cells

et al. 2010

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SUMMARYCoactivator-associated arginine methyltransferase I (CARM1; PRMT4) regulates gene expression by multiple mechanisms including methylation of histones and coactivation of steroid receptor transcription. Mice lacking CARM1 are small, fail to breathe and die shortly after birth, demonstrating the crucial role of CARM1 in development. In adults, CARM1 is overexpressed in human grade-III breast tumors and prostate adenocarcinomas, and knockdown of CARM1 inhibits proliferation of breast and prostate cancer cell lines. Based on these observations, we hypothesized that loss of CARM1 in mouse embryos would inhibit pulmonary cell proliferation, resulting in respiratory distress. By contrast, we report here that loss of CARM1 results in hyperproliferation of pulmonary epithelial cells during embryonic development. The lungs of newborn mice lacking CARM1 have substantially reduced airspace compared with their wild-type littermates. In the absence of CARM1, alveolar type II cells show increased proliferation. Electron microscopic analyses demonstrate that lungs from mice lacking CARM1 have immature alveolar type II cells and an absence of alveolar type I cells. Gene expression analysis reveals a dysregulation of cell cycle genes and markers of differentiation in the Carm1 knockout lung. Furthermore, there is an overlap in gene expression in the Carm1 knockout and the glucocorticoid receptor knockout lung, suggesting that hyperproliferation and lack of maturation of the alveolar cells are at least in part caused by attenuation of glucocorticoid-mediated signaling. These results demonstrate for the first time that CARM1 inhibits pulmonary cell proliferation and is required for proper differentiation of alveolar cells. ) are small and have defects in the differentiation of multiple cell types including T cells and adipocytes (Kim et al., 2004;Yadav et al., 2008;Yadav et al., 2003). Recently, it has been shown that mice carrying the enzyme-dead form of CARM1 phenocopy the Carm1 knockout, suggesting that CARM1 requires enzymatic activity for its known cellular functions (Kim et al., 2009). Carm1 knockout animals die shortly after birth and suffer from respiratory distress. Carm1/ animals fail to inflate their lungs after birth, and have reduced alveolar air space compared with wild-type littermates. These observations suggest that CARM1 is an important regulator of lung development. However, detailed studies of CARM1 expression and function in lung have not been described. Development of the distal lung and alveolar sacculation are tightly regulated by a myriad of hormone signals and a cascade of interacting transcription factor pathways that are just beginning to be elucidated (Cardoso and Lu, 2006;Maeda et al., 2007). Progenitor cells in the distal lung differentiate to multiple types including Clara bronchiole epithelial cells and alveolar type II (AT2) cells. AT2 cells are cuboidal and located in the alveolar sacs that produce the surfactant required to reduce surface tension for these sacs to fill with air. AT2 cell...

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“…12 CARM1 acts as a coactivator of many transcription factors. 8,[13][14][15][16] Moreover, it was reported to methylate histone H3 at arginine 17 (H3R17), which correlates with transcriptional activation, 17 as well as a unique set of non-histone proteins. [18][19][20][21][22][23][24][25] Furthermore, besides its role in transcription regulation, CARM1 affects also mRNA alternative splicing by methylating the splicing factors CA150, SAP49, SmB, and U1C 26 and mRNA stability/degradation of some specific mRNAs bearing AU-rich elements at their 3′-untranslated regions by methylating the protein HuD.…”

Section: Introductionmentioning

confidence: 99%

CARM1 but not Its Enzymatic Activity Is Required for Transcriptional Coactivation of NF-κB-Dependent Gene Expression

Jayne

Rothgiesser

Hottiger

2009

Journal of Molecular Biology

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Dual role of the arginine methyltransferase CARM1 in the regulation of c‐Fos target genes

Cited by 21 publications

References 52 publications

Methylation specifies distinct estrogen-induced binding site repertoires of CBP to chromatin

Methylation specifies distinct estrogen-induced binding site repertoires of CBP to chromatin

CARM1 is required for proper control of proliferation and differentiation of pulmonary epithelial cells

CARM1 but not Its Enzymatic Activity Is Required for Transcriptional Coactivation of NF-κB-Dependent Gene Expression

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