Fy the individual role of C/EBPb proteins in breast cancer-related CDH3/P-cadherin gene, as well as to expand the limited characterization of the mechanisms and players that regulate this pro-invasive protein in breast cancer.Supporting InformationTable S1 Conditions of the primary antibodies.(PDF)Table S2 Primers sequences used in the differentassays. 25033180 (PDF)Author ContributionsConceived and designed the experiments: AA CR JP JCM RS FS. Performed the experiments: AA CR BS ARN ASR. Analyzed the data: AA JP FS. Contributed reagents/materials/analysis tools: AA CR JCM JP. Wrote the paper: AA JP FS.C/EBPb Targets CDH3 Gene in Breast Cancer Cells
Protein arginine methylation is a post-translational modification (PTM) that has 
been implicated in a large variety of important cellular functions such as signalling, DNA repair, RNA maturation and nucleocytoplasmic transport, protein protection, ribosomal assembly, and regulation of gene expression [1]. In mammalian cells arginine methylation is performed by a sequence-related family of protein arginine methyl 
transferases termed PRMTs. Given that this family of enzymes plays an integral role in many cellular processes, it is unsurprising that their dysregulation is involved in several human MC-LR diseases [1?]. Currently, nine different human PRMTs are known (PRMT1-9). PRMTs share a set of conserved sequence motifs and a THW (threonine-histidinetryptophan) loop, but differ in the MedChemExpress AZ-876 presence of additional protein domains, cellular localization, and tissue expression. There does not appear to be major redundancy between these enzymes since mouse knockouts display generally clear and dramatic phenotypes [1]. PRMT6 is a predominantly nuclear enzyme characterized by substrates specificity and by automethylation [5]. In particular, PRMT6 is the major PRMT responsible for histone H3R2 methylation and it has a clear role in antagonizing the MixedLineage Leukaemia (MLL)-complex-dependent methylation of theLys-4 residue [6?]. Methylation of H2AR29 is specifically enriched at genes repressed by PRMT6, implicating also this modification in transcriptional repression [9]. 1081537 In addition PRMT6 binds and methylates the architectural transcription factor HMGA1 [10,11]. These evidences underline an important function for this enzyme in the context of chromatin structure organization and epigenetic regulation. PRMT6 has shown to directly impact transcription, in fact thrombospondin-1 (TSP-1) was identified as a transcriptional repression target of PRMT6 by directly regulating the TSP-1 promoter activity [12]. Further involvement of PRMT6 in regulation of gene expression is provided by the coactivation of progesterone, glucocorticoid and oestrogen receptors [13]. Besides the involvement of PRMT6 in epigenetic and transcription, arginine methylation by PRMT6 was shown to have a negative impact on the activities of HIV-1 Tat, Rev and nucleocapsid proteins, thus potentially affecting HIV replication [14?7]. In addition, PRMT6 was demonstrated to specifically methylate DNA polymerase ?resulting in a strong stimulation of DNA polymerase activity by enhancing DNA binding and processivity, thus involving PRMT6 in base excision repair (BER) [18]. Very recently, PRMT6 was found to be involved in the control of cell cycle progression repressing key cell-cycle regulators, i.e. p21 (CDKN1a), p27 (CDKN1B), and p16 (CDKN2A) [19?1].The Protein-Protein Molecular Network of PRMTFor both p21 and p27, repression is concomitant with the presence o.Fy the individual role of C/EBPb proteins in breast cancer-related CDH3/P-cadherin gene, as well as to expand the limited characterization of the mechanisms and players that regulate this pro-invasive protein in breast cancer.Supporting InformationTable S1 Conditions of the primary antibodies.(PDF)Table S2 Primers sequences used in the differentassays. 25033180 (PDF)Author ContributionsConceived and designed the experiments: AA CR JP JCM RS FS. Performed the experiments: AA CR BS ARN ASR. Analyzed the data: AA JP FS. Contributed reagents/materials/analysis tools: AA CR JCM JP. Wrote the paper: AA JP FS.C/EBPb Targets CDH3 Gene in Breast Cancer Cells
Protein arginine methylation is a post-translational modification (PTM) that has been implicated in a large variety of important cellular functions such as signalling, DNA repair, RNA maturation and nucleocytoplasmic transport, protein protection, ribosomal assembly, and regulation of gene expression [1]. In mammalian cells arginine methylation is performed by a sequence-related family of protein arginine methyl transferases termed PRMTs. Given that this family of enzymes plays an integral role in many cellular processes, it is unsurprising that their dysregulation is involved in several human diseases [1?]. Currently, nine different human PRMTs are known (PRMT1-9). PRMTs share a set of conserved sequence motifs and a THW (threonine-histidinetryptophan) loop, but differ in the presence of additional protein domains, cellular localization, and tissue expression. There does not appear to be major redundancy between these enzymes since mouse knockouts display generally clear and dramatic phenotypes [1]. PRMT6 is a predominantly nuclear enzyme characterized by substrates specificity and by automethylation [5]. In particular, PRMT6 is the major PRMT responsible for histone H3R2 methylation and it has a clear role in antagonizing the MixedLineage Leukaemia (MLL)-complex-dependent methylation of theLys-4 residue [6?]. Methylation of H2AR29 is specifically enriched at genes repressed by PRMT6, implicating also this modification in transcriptional repression [9]. 1081537 In addition PRMT6 binds and methylates the architectural transcription factor HMGA1 [10,11]. These evidences underline an important function for this enzyme in the context of chromatin structure organization and epigenetic regulation. PRMT6 has shown to directly impact transcription, in fact thrombospondin-1 (TSP-1) was identified as a transcriptional repression target of PRMT6 by directly regulating the TSP-1 promoter activity [12]. Further involvement of PRMT6 in regulation of gene expression is provided by the coactivation of progesterone, glucocorticoid and oestrogen receptors [13]. Besides the involvement of PRMT6 in epigenetic and transcription, arginine methylation by PRMT6 was shown to have a negative impact on the activities of HIV-1 Tat, Rev and nucleocapsid proteins, thus potentially affecting HIV replication [14?7]. In addition, PRMT6 was demonstrated to specifically methylate DNA polymerase ?resulting in a strong stimulation of DNA polymerase activity by enhancing DNA binding and processivity, thus involving PRMT6 in base excision repair (BER) [18]. Very recently, PRMT6 was found to be involved in the control of cell cycle progression repressing key cell-cycle regulators, i.e. p21 (CDKN1a), p27 (CDKN1B), and p16 (CDKN2A) [19?1].The Protein-Protein Molecular Network of PRMTFor both p21 and p27, repression is concomitant with the presence o.