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Phospho Switch Triggers Brd4 Chromatin Binding and Activator Recruitment for Gene-Specific Targeting
Phosphorylation of Brd4 by CK2 enables Brd4 to bind chromatin and to recruit p53 to specific promoters
Although chromatin targeting is a crucial function of Bromodomain-containing protein 4 (Brd4), the regulation of how bromodomains bind to acetylated histones is not well understood, nor is the mechanism by which bromodomains acquire gene-specific activity. In this paper, researchers at the University of Texas Southwestern Medical Center use an interaction screen and domain mapping to show that Brd4 associates directly with many transcription factors and chromatin-modifying enzymes, such as p53, YY1, AP2, c-Jun, c-Myc/Max, C/EBPa, C/EBPb, Acf1, and G9a. Brd4-p53 association is shown to be modulated by casein kinase II (CK2)-mediated phosphorylation of a conserved acidic region in Brd4. This phospho switch mechanism dictates the ability of Brd4 to bind to chromatin and also to recruit p53 to regulated promoters. The study, therefore, “not only uncovers a molecular mechanism for gene-specific targeting by a universal epigenetic reader, but also identifies Brd4 as a regulator for p53 target gene transcription”.
Wu et al. (2013) Molecular Cell Published online Jan. 10. Abstract.
Active Motif antibodies cited in this paper:
Histone H3, C-terminal polyclonal antibody
Histone H3K4ac polyclonal antibody
Histone H3K4me2 polyclonal antibody
Histone H3K4me3 polyclonal antibody
Histone H3K9ac polyclonal antibody
Histone H3K9me2 polyclonal antibody
Histone H3K9me3 polyclonal antibody
Histone H3K18ac polyclonal antibody
Histone H3K27me2 polyclonal antibody
Histone H3K27me3 polyclonal antibody
Histone H4K5ac polyclonal antibody
Histone H4K12ac polyclonal antibody
Histone H4K16ac polyclonal antibody
Active Motif recombinant proteins cited in this paper:
Recombinant ABL1 protein, active
Recombinant AKT1 protein, active
Recombinant AKT2 protein, active
Recombinant AKT3 protein, active
Recombinant CHK1 protein, active
Recombinant CHK2 protein, active
Recombinant CSK protein, active
Recombinant ErbB-2 protein, active
Recombinant ErbB-4 protein, active
Recombinant ERK1 protein, active
Recombinant ERK2 protein, active
Recombinant FAK protein, active
Recombinant GSK3β protein, active
Recombinant HCK protein, active
Recombinant IKKβ protein, active
Recombinant IKKε protein, active
Recombinant JNK3 protein, active
Recombinant LCK protein, active
Recombinant MAPKAPK5 protein, active
Recombinant p38α protein, active
Recombinant PAK2 protein, active
Recombinant PAK4 protein, active
Recombinant PKA protein, active
Recombinant PKCα protein, active
Recombinant S6K protein, active
Recombinant SNK protein, active
Although chromatin targeting is a crucial function of Bromodomain-containing protein 4 (Brd4), the regulation of how bromodomains bind to acetylated histones is not well understood, nor is the mechanism by which bromodomains acquire gene-specific activity. In this paper, researchers at the University of Texas Southwestern Medical Center use an interaction screen and domain mapping to show that Brd4 associates directly with many transcription factors and chromatin-modifying enzymes, such as p53, YY1, AP2, c-Jun, c-Myc/Max, C/EBPa, C/EBPb, Acf1, and G9a. Brd4-p53 association is shown to be modulated by casein kinase II (CK2)-mediated phosphorylation of a conserved acidic region in Brd4. This phospho switch mechanism dictates the ability of Brd4 to bind to chromatin and also to recruit p53 to regulated promoters. The study, therefore, “not only uncovers a molecular mechanism for gene-specific targeting by a universal epigenetic reader, but also identifies Brd4 as a regulator for p53 target gene transcription”.
Wu et al. (2013) Molecular Cell Published online Jan. 10. Abstract.
Active Motif antibodies cited in this paper:
Histone H3, C-terminal polyclonal antibody
Histone H3K4ac polyclonal antibody
Histone H3K4me2 polyclonal antibody
Histone H3K4me3 polyclonal antibody
Histone H3K9ac polyclonal antibody
Histone H3K9me2 polyclonal antibody
Histone H3K9me3 polyclonal antibody
Histone H3K18ac polyclonal antibody
Histone H3K27me2 polyclonal antibody
Histone H3K27me3 polyclonal antibody
Histone H4K5ac polyclonal antibody
Histone H4K12ac polyclonal antibody
Histone H4K16ac polyclonal antibody
Active Motif recombinant proteins cited in this paper:
Recombinant ABL1 protein, active
Recombinant AKT1 protein, active
Recombinant AKT2 protein, active
Recombinant AKT3 protein, active
Recombinant CHK1 protein, active
Recombinant CHK2 protein, active
Recombinant CSK protein, active
Recombinant ErbB-2 protein, active
Recombinant ErbB-4 protein, active
Recombinant ERK1 protein, active
Recombinant ERK2 protein, active
Recombinant FAK protein, active
Recombinant GSK3β protein, active
Recombinant HCK protein, active
Recombinant IKKβ protein, active
Recombinant IKKε protein, active
Recombinant JNK3 protein, active
Recombinant LCK protein, active
Recombinant MAPKAPK5 protein, active
Recombinant p38α protein, active
Recombinant PAK2 protein, active
Recombinant PAK4 protein, active
Recombinant PKA protein, active
Recombinant PKCα protein, active
Recombinant S6K protein, active
Recombinant SNK protein, active
Germline DNA Demethylation Dynamics and Imprint Erasure Through 5-Hydroxymethylcytosine
Conversion of 5-mC to 5-hmC by TET1 and TET2 is followed by the decline of 5-hmC levels by replication-dependent dilution
Epigenetic reprogramming, characterized by the loss of CpG methylation and histone modifications, occurs in a sequential manner in primordial germ cells (PGCs) to generate totipotency. As the dynamics and underlying mechanism of this process is poorly characterized, the authors performed a comprehensive analysis of PGCs to address the mechanistic basis of epigenetic reprogramming. They not only demonstrate that the depletion of cytosine methylation (5-mC), including imprint erasure, occurs via the conversion to 5-hydroxymethylcytosine (5-hmC), but also that this process is driven by TET1 and TET2 in mouse PGCs. The rate of progressive decline in 5-hmC was shown to be consistent with a replication-dependent mechanism towards a completely unmodified state. In essence, reprogramming in PGCs involves multiple redundant mechanisms to reset the genome for totipotency, emphasizing the comprehensive nature of DNA demethylation in PGCs.
Hacket et al. (2013) Science 339(6118):448-452. Abstract.
Active Motif products cited in this paper:
5-Hydroxymethylcytosine (5-hmC) antibodies
5-Formylcytosine (5-fC) antibodies
5-Carboxylcytosine (5-caC) antibodies
Active Motif products relevant to this paper:
5-Methylcytosine (5-mC) antibodies
Recombinant Tet1 protein
Tet2 monoclonal antibody
Tet3 polyclonal antibody
Epigenetic reprogramming, characterized by the loss of CpG methylation and histone modifications, occurs in a sequential manner in primordial germ cells (PGCs) to generate totipotency. As the dynamics and underlying mechanism of this process is poorly characterized, the authors performed a comprehensive analysis of PGCs to address the mechanistic basis of epigenetic reprogramming. They not only demonstrate that the depletion of cytosine methylation (5-mC), including imprint erasure, occurs via the conversion to 5-hydroxymethylcytosine (5-hmC), but also that this process is driven by TET1 and TET2 in mouse PGCs. The rate of progressive decline in 5-hmC was shown to be consistent with a replication-dependent mechanism towards a completely unmodified state. In essence, reprogramming in PGCs involves multiple redundant mechanisms to reset the genome for totipotency, emphasizing the comprehensive nature of DNA demethylation in PGCs.
Hacket et al. (2013) Science 339(6118):448-452. Abstract.
Active Motif products cited in this paper:
5-Hydroxymethylcytosine (5-hmC) antibodies
5-Formylcytosine (5-fC) antibodies
5-Carboxylcytosine (5-caC) antibodies
Active Motif products relevant to this paper:
5-Methylcytosine (5-mC) antibodies
Recombinant Tet1 protein
Tet2 monoclonal antibody
Tet3 polyclonal antibody
Loss of BAP1 Causes Myeloid Transformation
Hematopoietic-restricted deletion of BAP1 in mice recapitulates human myelodysplastic syndrome
Somatic inactivating mutations in BAP1 have been identified in many cancers. Researchers at Genentech have now shown that knockout of BAP1 within the hematopoietic compartment is sufficient for the development of myeloid leukemia, thus solidifying the role of BAP1 as a tumor suppressor. In an effort to understand the mechanism of tumor suppression, the BAP1 interacting proteins HCF, OGT, ASXL1 and others were identified by BAP1 pull-down followed by Mass Spec. The supporting ChIP-Seq data, generated at Active Motif, identified BAP1 binding sites across the genome, and OGT and HCF1 ChIP-Seq showed a high level of co-occupancy with BAP1.
Dey et al. (2012) Science 337(6101):1541-1546. Abstract.
Active Motif products cited in this paper:
ChIP-Sequencing Service (ChIP-Seq)
Active Motif products relevant to this paper:
OGT/O-GlcNAc transferase polyclonal antibody
Somatic inactivating mutations in BAP1 have been identified in many cancers. Researchers at Genentech have now shown that knockout of BAP1 within the hematopoietic compartment is sufficient for the development of myeloid leukemia, thus solidifying the role of BAP1 as a tumor suppressor. In an effort to understand the mechanism of tumor suppression, the BAP1 interacting proteins HCF, OGT, ASXL1 and others were identified by BAP1 pull-down followed by Mass Spec. The supporting ChIP-Seq data, generated at Active Motif, identified BAP1 binding sites across the genome, and OGT and HCF1 ChIP-Seq showed a high level of co-occupancy with BAP1.
Dey et al. (2012) Science 337(6101):1541-1546. Abstract.
Active Motif products cited in this paper:
ChIP-Sequencing Service (ChIP-Seq)
Active Motif products relevant to this paper:
OGT/O-GlcNAc transferase polyclonal antibody
