RESUMO
Transcription factors play a key role in maintaining cell identity. One mechanism of such cell memory after multiple rounds of cell division cycles is through persistent mitotic chromosome binding, although how individual transcription factors achieve mitotic chromosome retention is not completely understood. Here we show that PAX6, a lineage-determining transcription factor, coats mitotic chromosomes. Using deletion and point mutants associated with human ocular diseases in live-cell imaging analysis, we identified two regions, MCR-D1 and MCR-D2, that were responsible for mitotic chromosome retention of PAX6. We also identified three nuclear localization signals (NLSs) that contributed to mitotic chromosome retention independent of their nuclear import functions. Full mitotic chromosome retention required the presence of DNA-binding domains as well as NLSs within MCR-Ds. Furthermore, disease-associated mutations and NLS mutations changed the distribution of intrinsically disordered regions (IDRs) in PAX6. Our findings not only identify PAX6 as a novel mitotic chromosome retention factor but also demonstrate that the mechanism of mitotic chromosome retention involves sequence-specific DNA binding, NLSs, and molecular conformation determined by IDRs. These findings link mitotic chromosome retention with PAX6-related pathogenesis and imply similar mechanisms for other lineage-determining factors in the PAX family.
Assuntos
Cromossomos Humanos/metabolismo , Oftalmopatias/genética , Mitose/genética , Fator de Transcrição PAX6/metabolismo , Células HEK293 , Humanos , Microscopia Intravital , Mutação , Fator de Transcrição PAX6/genéticaRESUMO
Heterochromatin, a type of condensed DNA in eukaryotic cells, has two main categories: Constitutive heterochromatin, which contains H3K9 methylation, and facultative heterochromatin, which contains H3K27 methylation. Methylated H3K9 and H3K27 serve as docking sites for chromodomain-containing proteins that compact chromatin. M33 (also known as CBX2) is a chromodomain-containing protein that binds H3K27me3 and compacts chromatin in vitro. However, whether M33 mediates chromatin compaction in cellulo remains unknown. Here we show that M33 compacts chromatin into DAPI-intense heterochromatin domains in cells. The formation of these heterochromatin domains requires H3K27me3, which recruits M33 to form nuclear bodies. G9a and SUV39H1 are sequentially recruited into M33 nuclear bodies to create H3K9 methylated chromatin in a process that is independent of HP1α. Finally, M33 decreases progerin-induced nuclear envelope disruption caused by loss of heterochromatin. Our findings demonstrate that M33 mediates the formation of condensed chromatin by forming nuclear bodies containing both H3K27me3 and H3K9me3. Our model of M33-dependent chromatin condensation suggests H3K27 methylation corroborates with H3K9 methylation during the formation of facultative heterochromatin and provides the theoretical basis for developing novel therapies to treat heterochromatin-related diseases.
Assuntos
Cromatina/metabolismo , Histonas/metabolismo , Lisina/metabolismo , Proteínas Nucleares/metabolismo , Complexo Repressor Polycomb 1/metabolismo , Células Cultivadas , Homólogo 5 da Proteína Cromobox , Células HEK293 , Humanos , MetilaçãoRESUMO
OBJECTIVE: To compare long-term clinical outcomes between patients with heart failure due to non-ischemic cardiomyopathy (NICM) and those due to ischemic cardiomyopathy (ICM) after cardiac resynchronization therapy (CRT). METHODS AND RESULTS: EMbase, PubMed, and Cochrane Library were searched for published studies up to December 2017. Twenty-one observational studies with 12,331 patients were enrolled in the present meta-analysis. The results demonstrated that the all-cause mortality in NICM patients was significantly lower than that in ICM patients (RR 1.37, 95% CI 1.16-1.61). In terms of echocardiographic parameters, NICM patients exhibited statistically significant improvement in left ventricular ejection fraction (LVEF) (MD 2.70, 95%CI -4.13 to -1.28), and a significant decrement in left ventricular end-systolic volume (LVESV) (MD 10.41,95% CI 2.10-18.73) and left ventricular end diastolic diameter (LVEDD) (MD 7.63, 95% CI 2.59-12.68) as compared with ICM patients. No significant difference was observed in the improvement of New York Heart Association Functional Classification (MD 0.05, 95% CI -0.05 to 0.15), pulmonary arterial systolic pressure (PASP) (MD -0.61, 95% CI -4.36 to 3.14), and severity of mitral regurgitation (MD 0.00, 95% CI -0.08 to 0.07) between the 2 groups. CONCLUSIONS: Our meta-analysis illustrated that patients with HF due to NICM tended to have better clinical outcomes and LV reverse remodeling as compared with those due to ICM. This finding may help clinicians select patients who respond favorably to CRT, though further research is required to clarify the potential confounding factors and underlying mechanisms for this phenomenon.
Assuntos
Terapia de Ressincronização Cardíaca/mortalidade , Insuficiência Cardíaca/etiologia , Isquemia Miocárdica/complicações , Idoso , Causas de Morte , Feminino , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/fisiopatologia , Estudos Observacionais como Assunto , Volume Sistólico , Resultado do Tratamento , Função Ventricular Esquerda , Remodelação VentricularRESUMO
Promyelocytic leukemia nuclear bodies (PML-NBs) are PML-based nuclear structures that regulate various cellular processes. SUMOylation, the process of covalently conjugating small ubiquitin-like modifiers (SUMOs), is required for both the formation and the disruption of PML-NBs. However, detailed mechanisms of how SUMOylation regulates these processes remain unknown. Here we report that SUMO5, a novel SUMO variant, mediates the growth and disruption of PML-NBs. PolySUMO5 conjugation of PML at lysine 160 facilitates recruitment of PML-NB components, which enlarges PML-NBs. SUMO5 also increases polySUMO2/3 conjugation of PML, resulting in RNF4-mediated disruption of PML-NBs. The acute promyelocytic leukemia oncoprotein PML-RARα blocks SUMO5 conjugation of PML, causing cytoplasmic displacement of PML and disruption of PML-NBs. Our work not only identifies a new member of the SUMO family but also reveals the mechanistic basis of the PML-NB life cycle in human cells.
Assuntos
Núcleo Celular/metabolismo , Lisina/metabolismo , Proteína da Leucemia Promielocítica/genética , Proteína da Leucemia Promielocítica/metabolismo , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/metabolismo , Animais , Linhagem Celular Tumoral , Núcleo Celular/genética , Clonagem Molecular , Regulação da Expressão Gênica , Células HEK293 , Células HeLa , Humanos , Células K562 , Células MCF-7 , Camundongos , Células NIH 3T3 , Proteínas Nucleares/metabolismo , Especificidade de Órgãos , Proteína da Leucemia Promielocítica/química , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/genética , Sumoilação , Fatores de Transcrição/metabolismo , Ubiquitinas/metabolismoRESUMO
PAX3 is a transcription factor critical to gene regulation in mammalian development. Mutations in PAX3 are associated with Waardenburg syndrome (WS), but the mechanism of how mutant PAX3 proteins cause WS remains unclear. Here, we found that PAX3 loads on mitotic chromosomes using its homeodomain. PAX3 WS mutants with mutations in homeodomain lose the ability to bind mitotic chromosomes. Moreover, loading of PAX3 on mitotic chromosomes requires arginine methylation, which is regulated by methyltransferase PRMT5 and demethylase JMJD6. Mutant PAX3 proteins that lose mitotic chromosome localization block cell proliferation and normal development of zebrafish. These results reveal the molecular mechanism of PAX3s loading on mitotic chromosomes and the importance of this localization pattern in normal development. Our findings suggest that PAX3 WS mutants interfere with the normal functions of PAX3 in a dominant negative manner, which is important to the understanding of the pathogenesis of Waardenburg syndrome.
Assuntos
Arginina/metabolismo , Cromossomos Humanos , Mitose/genética , Fatores de Transcrição Box Pareados/genética , Síndrome de Waardenburg/genética , Animais , Células HEK293 , Humanos , Larva/metabolismo , Metilação , Fator de Transcrição PAX3 , Proteína-Arginina N-Metiltransferases/metabolismo , Peixe-Zebra/crescimento & desenvolvimentoRESUMO
BACKGROUND: Proper re-establishment of heterochromatin after each round of DNA replication is critical to the preservation of cell identity. Paired box 3 (PAX3), a transcription factor important in embryonic development, was found to mediate the formation of pericentromeric heterochromatin. However, how PAX3 recognizes the heterochromatic environment and re-establishes it after DNA replication remains unclear. MATERIALS AND METHODS: Cell-cycle synchronization, fluorescence microscopic analyses, and co-immunoprecipitation were used to analyze the heterochromatic localization of PAX3 in HEK 293 cells and NIH 3T3 cells. RESULTS: We found that PAX3 binds pericentromeric heterochromatin during middle-to-late S phase. Loading of PAX3 onto pericentromeric heterochromatin requires poly(ADP-ribose) polymerase 1 (PARP1). Furthermore, loss of PAX3 or PARP1 delays cell-cycle progression through the S phase. CONCLUSION: Our results reveal how PAX3 recognizes and maintains pericentromeric heterochromatin at the S phase of the cell cycle.
Assuntos
Heterocromatina/metabolismo , Fatores de Transcrição Box Pareados/metabolismo , Poli(ADP-Ribose) Polimerases/metabolismo , Fase S , Animais , Ciclo Celular , Células HEK293 , Heterocromatina/genética , Humanos , Camundongos , Células NIH 3T3 , Fatores de Transcrição Box Pareados/genética , Ligação Proteica , Transporte Proteico , Proteínas Recombinantes de Fusão/metabolismoRESUMO
Aberrant expression levels of transcriptional regulators result in alterations in transcriptional control. STAF65γ is a structural subunit of the GCN5 transcriptional co-activator complex. Reports showed that STAF65γ is highly expressed in several human cancer cells, but the consequences of this aberrant expression pattern remain elusive. Here, we show that the STAF65γ protein is highly expressed in lung adenocarcinoma patients and high levels of STAF65γ correlate with poor prognosis. High levels of STAF65γ cause repression of the c-Myc oncogene through physical association with transcription factor YY1 and co-repressors HDACs. Physical interactions between STAF65γ and class IIa HDACs facilitate nuclear enrichment and regulate the assembly of HDAC complexes. Moreover, SUMOylation of STAF65γ is necessary for maintaining the co-repressor complex containing YY1 and class IIa HDACs at the promoter. Our findings reveal a distinct role of STAF65γ in nuclear import, transcriptional repression, and cell cycle regulation at high levels of expression, which is associated with poor clinical outcomes of lung adenocarcinoma.
Assuntos
Adenocarcinoma/genética , Histona Desacetilases/genética , Neoplasias Pulmonares/genética , Regiões Promotoras Genéticas , Transativadores/genética , Transcrição Gênica , Transporte Ativo do Núcleo Celular/genética , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Adulto , Idoso , Ciclo Celular/genética , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteínas Repressoras/genética , Sumoilação , Fator de Transcrição YY1/genéticaRESUMO
Poly(ADP-ribose) polymerase-2 (PARP-2) catalyzes poly(ADP-ribosyl)ation (PARylation) and regulates numerous nuclear processes, including transcription. Depletion of PARP-2 alters the activity of transcription factors and global gene expression. However, the molecular action of how PARP-2 controls the transcription of target promoters remains unclear. Here we report that PARP-2 possesses transcriptional repression activity independently of its enzymatic activity. PARP-2 interacts and recruits histone deacetylases HDAC5 and HDAC7, and histone methyltransferase G9a to the promoters of cell cycle-related genes, generating repressive chromatin signatures. Our findings propose a novel mechanism of PARP-2 in transcriptional regulation involving specific protein-protein interactions and highlight the importance of PARP-2 in the regulation of cell cycle progression.
Assuntos
Ciclo Celular/genética , Regulação da Expressão Gênica , Histonas/metabolismo , Poli Adenosina Difosfato Ribose/metabolismo , Poli(ADP-Ribose) Polimerases/metabolismo , Fase G1/genética , Células HEK293 , Antígenos de Histocompatibilidade/metabolismo , Histona Desacetilases/metabolismo , Histona-Lisina N-Metiltransferase/metabolismo , Humanos , Metilação , Poli(ADP-Ribose) Polimerases/genética , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas c-myc/genética , Fator de Transcrição YY1/metabolismoRESUMO
OBJECTIVE: To assess the correlation between polymorphisms in the coagulation factor VII (F VII)gene hypervariable region 4 (HVR4)site and risk related to coronary heart disease (CHD)in different ethnic populations, especially the Asian populations. METHODS: Publications up to April 2013, from CBM, CNKI, Wanfang Database,VIP, PubMed, Cochrane Library and Embase were searched to collect data from case-control studies related to F VII gene HVR4 site and CHD in populations from different ethnicities. Quality of studies was evaluated, available data extracted and both RevMan 5.1 and Stata 11.0 softwares were used for Meta-analysis. RESULTS: Fifteen case-control studies were included, involving 3167 cases with CHD group and 3168 cases in the control group. RESULTS: on this Meta-analysis showed that:a)polymorphism of the F VII gene HVR4 site H7/H6+H5 and CHD, b)H7H7/H6H6 + H7H6 and CHD were both slightly correlated between people with different ethnic backgrounds. However, the H6 allele versus H7+H5 allele and CHD showed different results-a high correlation seen in different ethnic groups. H5 allele versus H6+H7 allele and CHD did not appear significant difference(OR = 1.20, 95%CI:0.76-1.90, P = 0.43). CONCLUSION: Both F VII gene HVR4 polymorphisms H7 allele and the H7H7 genotype might have served as protective factors for CHD in different ethnic groups, H6 allele might serve as a risk factor for CHD, but H5 allele was likely not to be associated with CHD in different ethnic groups.
Assuntos
Doença das Coronárias/genética , Fator VII/genética , Polimorfismo Genético , Alelos , Frequência do Gene , Genótipo , Humanos , Fatores de RiscoRESUMO
FK506-binding proteins (FKBPs) are intracellular receptors for FK506 and rapamycin, immunosuppressants that have recently been utilized as anticancer drugs. In the cytoplasm, FKBPs and these drugs modulate signal transduction pathways. However, recent reports reveal novel functions of FKBPs in the nucleus, which include regulation of transcription factors, histone chaperone activity, and modifications of chromatin structure. These activities are known to affect gene expression, DNA repair, and DNA replication. Therefore, elucidation of the nuclear functions of FKBPs will help researchers and clinicians better understand how immunosuppressants work as anticancer drugs, which might in turn lead to novel designs of cancer therapy.
Assuntos
Cromatina/metabolismo , Neoplasias/patologia , Proteínas de Ligação a Tacrolimo/metabolismo , Animais , Antineoplásicos/farmacologia , Desenho de Fármacos , Humanos , Imunossupressores/farmacologia , Transdução de Sinais , Sirolimo/farmacologia , Tacrolimo/farmacologiaRESUMO
Acetylation of lysines is a prominent form of modification in mammalian proteins. Deacetylation of proteins is catalyzed by histone deacetylases, traditionally named after their role in histone deacetylation, transcriptional modulation, and epigenetic regulation. Despite the link between histone deacetylases and chromatin structure, some of the histone deacetylases reside in various compartments in the cytoplasm. Here, we review how these cytoplasmic histone deacetylases are regulated, the identification of nonhistone substrates, and the functional implications of their nondeacetylase enzymatic activities.
Assuntos
Citoplasma/enzimologia , Histona Desacetilases/metabolismo , Animais , Histonas/metabolismo , Humanos , Sirtuínas/metabolismo , Especificidade por SubstratoRESUMO
HDAC10 belongs to the class II histone deacetylase family; however, its functions remain enigmatic. We report here that the HDAC10 protein complex contained deacetylated chaperone protein hsc70, and HDAC10 relieved repression of melanogenesis by decreasing the repressional activity of two transcriptional regulators, paired box protein 3 (Pax3) and KRAB-associated protein 1 (KAP1). HDAC10 physically interacted with Pax3 and KAP1 in a ternary complex and maintained Pax3 and KAP1 in a deacetylated state. Deacetylated Pax3 and KAP1 derepressed promoters of microphthalmia-associated transcription factor (MITF) and melanocyte-specific tyrosinase-related protein 1 and 2 (TRP-1 and TRP-2), three genes of the melanogenesis cascade, in a trichostatin A-sensitive manner. Co-occupancy of melanogenic promoters by HDAC10, Pax3, and KAP1 only happened in cells of the melanocyte lineage, and KAP1 facilitated nuclear enrichment of HDAC10. Finally, cellular melanin content correlated directly with the expression level and activity of HDAC10. Our results not only show that HDAC10 regulates melanogenesis but also demonstrate that the transcriptional activities of Pax3 and KAP1 are intimately linked to their acetylation status.
Assuntos
Regulação da Expressão Gênica , Proteínas de Choque Térmico HSC70/metabolismo , Histona Desacetilases/metabolismo , Melaninas/biossíntese , Fatores de Transcrição Box Pareados/metabolismo , Proteínas Repressoras/metabolismo , Linhagem Celular , Proteínas de Choque Térmico HSC70/genética , Histona Desacetilases/genética , Humanos , Oxirredutases Intramoleculares/genética , Oxirredutases Intramoleculares/metabolismo , Melaninas/genética , Fator de Transcrição Associado à Microftalmia/genética , Fator de Transcrição Associado à Microftalmia/metabolismo , Complexos Multiproteicos/metabolismo , Oxirredutases/genética , Oxirredutases/metabolismo , Fator de Transcrição PAX3 , Fatores de Transcrição Box Pareados/genética , Regiões Promotoras Genéticas , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Proteínas Repressoras/genética , Proteína 28 com Motivo TripartidoRESUMO
TRIP-Brs are a recently discovered set of proteins whose functions remain poorly characterized. Here we report the identification of TRIP-Br3 as a member of the TRIP-Br family along with evidence showing that TRIP-Brs interact with bromodomain-containing transcriptional cofactors PCAF, STAF65gamma, and KAP1. PCAF, a histone acetyltransferase; STAF65gamma, a protein associated with histone acetylation activity; and KAP1, a corepressor, influence the transcriptional activity of TRIP-Brs differentially. Finally, while all three TRIP-Brs are localized to the nucleus, TRIP-Br2 and TRIP-Br3 are also present in the cytoplasm through interaction with CRM1. Our results suggest that different TRIP-Brs function by interacting with a wide variety of bromodomain-containing transcriptional regulators in different subcellular locales.
Assuntos
Proteínas de Ciclo Celular/metabolismo , Núcleo Celular/metabolismo , Citoplasma/metabolismo , Proteínas Nucleares/metabolismo , Transativadores/metabolismo , Ativação Transcricional , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Sítios de Ligação/genética , Western Blotting , Proteínas de Ciclo Celular/genética , Linhagem Celular , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Ácidos Graxos Insaturados/farmacologia , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Células HeLa , Histona Acetiltransferases/genética , Histona Acetiltransferases/metabolismo , Humanos , Imunoprecipitação , Microscopia de Fluorescência , Proteínas Nucleares/genética , Ligação Proteica , Mapeamento de Interação de Proteínas/métodos , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Transativadores/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteína 28 com Motivo Tripartido , Fatores de Transcrição de p300-CBPRESUMO
Pax3 is a transcription factor crucial for normal development and tumorigenesis. Pax3 has been known to cause Waardenburg syndrome and pediatric alveolar rhabdomyosarcoma, but how Pax3 regulates transcription is not clear. Here, we report that Pax3 represses transcription and selectively interacts with heterochromatin protein 1 (HP1) and KAP1. KAP1 functions as a transcriptional corepressor by recruiting HP1 to facilitate the formation of a closed chromatin through histone deacetylation and methylation. We found that KAP1 is a corepressor for Pax3 by augmenting the repressional activity of Pax3. Unexpectedly, HP1gamma diminishes the repressional activity of Pax3. On target promoters, KAP1 and HP1gamma compete for binding with Pax3 on the N-terminal paired domain, and the C-terminal domain of Pax3 governs the subcellular localization of Pax3. Taken together, our results indicate that Pax3 represses transcription through a novel mechanism involving competition between corepressor KAP1 and the heterochromatin-binding protein HP1gamma.
Assuntos
Proteínas Cromossômicas não Histona/fisiologia , Proteínas de Ligação a DNA/fisiologia , Proteínas Nucleares/fisiologia , Fatores de Transcrição Box Pareados/genética , Proteínas Repressoras/fisiologia , Fatores de Transcrição/fisiologia , Transcrição Gênica , Animais , Homólogo 5 da Proteína Cromobox , Proteínas Cromossômicas não Histona/metabolismo , Proteínas de Ligação a DNA/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos ICR , Modelos Genéticos , Proteínas Nucleares/metabolismo , Fator de Transcrição PAX3 , Fatores de Transcrição Box Pareados/biossíntese , Ligação Proteica , Estrutura Terciária de Proteína , Proteínas Repressoras/metabolismo , Fatores de Transcrição/metabolismo , Transfecção , Proteína 28 com Motivo TripartidoAssuntos
Histona Desacetilases/isolamento & purificação , Histona Desacetilases/metabolismo , Animais , Vetores Genéticos , Células HeLa , Histona Desacetilases/genética , Humanos , Insetos , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismo , Sitios de Sequências Rotuladas , Transfecção/métodosRESUMO
The metastasis-associated protein MTA1 has been shown to express differentially to high levels in metastatic cells. MTA2, which is homologous to MTA1, is a component of the NuRD ATP-dependent chromatin remodeling and histone deacetylase complex. Here we report evidence that although both human MTA1 and MTA2 repress transcription specifically, are located in the nucleus, and contain associated histone deacetylase activity, they exist in two biochemically distinct protein complexes and may perform different functions pertaining to tumor metastasis. Specifically, both MTA1 and MTA2 complexes exert histone deacetylase activity. However, the MTA1 complex contained HDAC1/2, RbAp46/48, and MBD3, but not Sin3 or Mi2, two important components of the MTA2 complex. Moreover, the MTA2 complex is similar to the HDAC1 complex, suggesting a housekeeping role of the MTA2 complex. The MTA1 complex could be further separated, resulting in a core MTA1-HDAC complex, showing that the histone deacetylase activity and transcriptional repression activity were integral properties of the MTA1 complex. Finally, MTA1, unlike MTA2, did not interact with the pleotropic transcription factor YY1 or the immunophilin FKBP25. We suggest that MTA1 associates with a different set of transcription factors from MTA2 and that this property may contribute to the metastatic potential of cells overexpressing MTA1. We also report the finding of human MTA3, which is highly homologous to both MTA1 and MTA2. However, MTA3 does not repress transcription to a significant level and appears to have a diffused pattern of subcellular localization, suggesting a biological role distinct from that of the other two MTA proteins.
Assuntos
Histona Desacetilases/metabolismo , Proteínas Nucleares/metabolismo , Humanos , Proteínas de Neoplasias , Proteínas Nucleares/isolamento & purificação , Ligação Proteica , Proteínas Repressoras/metabolismo , Alinhamento de Sequência , Homologia de Sequência , Transativadores , Fatores de Transcrição/metabolismoRESUMO
Methylation of specific residues within the N-terminal histone tails plays a critical role in regulating eukaryotic gene expression. Although great advances have been made toward identifying histone methyltransferases (HMTs) and elucidating the consequences of histone methylation, little is known about the recruitment of HMTs to regulatory regions of chromatin. Here we report that the sequence-specific DNA-binding transcription factor Yin Yang 1 (YY1) binds to and recruits the histone H4 (Arg 3)-specific methyltransferase, PRMT1, to a YY1-activated promoter. Our data confirm that histone methylation does not occur randomly but rather is a targeted event and provides one mechanism by which HMTs can be recruited to chromatin to activate gene expression.