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Joomyeong Kim - One of the best experts on this subject based on the ideXlab platform.

  • oxytocin receptor is regulated by peg3
    PLOS ONE, 2018
    Co-Authors: Wesley D. Frey, Kaustubh Sharma, Terri L Cain, Katsuhiko Nishimori, Ryoichi Teruyama, Joomyeong Kim
    Abstract:

    Mouse Peg3 encodes a DNA-Binding protein involved in the milk letdown process. In the current study, we tested whether PEG3 controls the expression of the oxytocin receptor gene. According to the results, PEG3 directly binds to a genomic region within the 3rd exon of Oxtr, which contains a DNA-Binding Motif for PEG3. In nursing female mice, removal of PEG3 resulted in the increased expression of Oxtr in mammary epithelial cells and also in the hypothalamus. This suggests a repressor role of PEG3 in the expression of Oxtr in these tissues. Overall, this study suggests that Peg3 may function as a direct transcriptional regulator for Oxtr expression that acts to moderate the milk letdown process.

  • DNA-Binding Motif of the Imprinted Transcription Factor PEG3.
    PLOS ONE, 2015
    Co-Authors: Suman Lee, Joomyeong Kim
    Abstract:

    Peg3 is an imprinted gene that is predicted to encode a DNA-Binding zinc finger protein. This was previously demonstrated through Chromatin ImmunoPrecipitation-based Sequencing experiments. In the current study, we reanalyzed the previous ChIP-Seq results and further characterized the DNA-Binding Motif of PEG3. According to the results, PEG3 binds to the promoters and enhancers of a subset of genes that are closely associated with the known functions of Peg3. Some of these identified targets include Tufm, Mrpl45, Cry2, Per1, Slc25a29 and Slc38a2. With this set of targets, we derived a DNA-Binding Motif of PEG3, 5’-GTGGCAGT-3’, which also provides a tabulated matrix that can be used for predicting other unknown genomic targets. Among the newly identified targets, we analyzed in detail the two loci, Slc38a2 and Slc38a4, which are known to be involved in neutral amino acid transport. The results indicated that PEG3 likely functions as a transcriptional repressor for these two loci. Overall, the current study provides a set of genomic targets and also redefines the DNA-Binding Motif for the imprinted transcription factor PEG3.

  • DNA-Binding Motif and target genes of the imprinted transcription factor PEG3.
    Gene, 2012
    Co-Authors: Michelle M. Thiaville, Jennifer M. Huang, Hana Kim, Muhammad B. Ekram, Tae-young Roh, Joomyeong Kim
    Abstract:

    The Peg3 gene is expressed only from the paternally inherited allele located on proximal mouse chromosome 7. The PEG3 protein encoded by this imprinted gene is predicted to bind DNA based on its multiple zinc finger Motifs and nuclear localization. In the current study, we demonstrated PEG3's DNA-Binding ability by characterizing its Binding Motif and target genes. We successfully identified target regions bound by PEG3 from mouse brain extracts using chromatin immunoprecipitation analysis. PEG3 was demonstrated to bind these candidate regions through the consensus DNA-Binding Motif AGTnnCnnnTGGCT. In vitro promoter assays established that PEG3 controls the expression of a given gene through this Motif. Consistent with these observations, the transcriptional levels of a subset of the target genes are also affected in a mutant mouse model with reduced levels of PEG3 protein. Overall, these results confirm PEG3 as a DNA-Binding protein controlling specific target genes that are involved in distinct cellular functions.

Nikola P Pavletich - One of the best experts on this subject based on the ideXlab platform.

  • crystal structure of a smad mh1 domain bound to DNA
    Cell, 1998
    Co-Authors: Yanfei Wang, Haijuan Yang, Joan Massagué, Lata Jayaraman, Nikola P Pavletich
    Abstract:

    Abstract The Smad family of proteins, which are frequently targeted by tumorigenic mutations in cancer, mediate TGF-β signaling from cell membrane to nucleus. The crystal structure of a Smad3 MH1 domain bound to an optimal DNA sequence determined at 2.8 A resolution reveals a novel DNA-Binding Motif. In the crystals, base-specific DNA recognition is provided exclusively by a conserved 11-residue β hairpin that is embedded in the major groove of DNA. A surface loop region, to which tumorigenic mutations map, has been identified as a functional surface important for Smad activity. This structure establishes a framework for understanding how Smad proteins may act in concert with other transcription factors in the regulation of TGF-β-responsive genes.

  • crystal structure of a smad mh1 domain bound to DNA insights on DNA Binding in tgf beta signaling
    Cell, 1998
    Co-Authors: Yigong Shi, Haijuan Yang, Joan Massagué, Lata Jayaraman, Yanfei Wang, Nikola P Pavletich
    Abstract:

    Abstract The Smad family of proteins, which are frequently targeted by tumorigenic mutations in cancer, mediate TGF-β signaling from cell membrane to nucleus. The crystal structure of a Smad3 MH1 domain bound to an optimal DNA sequence determined at 2.8 A resolution reveals a novel DNA-Binding Motif. In the crystals, base-specific DNA recognition is provided exclusively by a conserved 11-residue β hairpin that is embedded in the major groove of DNA. A surface loop region, to which tumorigenic mutations map, has been identified as a functional surface important for Smad activity. This structure establishes a framework for understanding how Smad proteins may act in concert with other transcription factors in the regulation of TGF-β-responsive genes.

  • zinc finger DNA recognition crystal structure of a zif268 DNA complex at 2 1 a
    Science, 1991
    Co-Authors: Nikola P Pavletich, Carl O Pabo
    Abstract:

    The zinc finger DNA-Binding Motif occurs in many proteins that regulate eukaryotic gene expression. The crystal structure of a complex containing the three zinc fingers from Zif268 (a mouse immediate early protein) and a consensus DNA-Binding site has been determined at 2.1 angstroms resolution and refined to a crystallographic R factor of 18.2 percent. In this complex, the zinc fingers bind in the major groove of B-DNA and wrap part way around the double helix. Each finger has a similar relation to the DNA and makes its primary contacts in a three-base pair subsite. Residues from the amino-terminal portion of an alpha helix contact the bases, and most of the contracts are made with the guanine-rich strand of the DNA. This structure provides a framework for understanding how zinc fingers recognize DNA and suggests that this Motif may provide a useful basis for the design of novel DNA-Binding proteins.

Barbara J. Graves - One of the best experts on this subject based on the ideXlab platform.

  • solution structure of the ets domain from murine ets 1 a winged helix turn helix DNA Binding Motif
    The EMBO Journal, 1996
    Co-Authors: Logan W Donaldson, Barbara J. Graves, Jeannine M Petersen, Lawrence P. Mcintosh
    Abstract:

    Ets-1 is the prototypic member of the ets family of transcription factors. This family is characterized by the conserved ETS domain that mediates specific DNA Binding. Using NMR methods, we have determined the structure of a fragment of murine Ets-1 composed of the 85 residue ETS domain and a 25 amino acid extension that ends at its native C-terminus. The ETS domain folds into a helix-turn-helix Motif on a four-stranded anti-parallel beta-sheet scaffold. This structure places Ets-1 in the winged helix-turn-helix (wHTH) family of DNA Binding proteins and provides a model for interpreting the sequence conservation of the ETS domain and the specific interaction of Ets-1 with DNA. The C-terminal sequence of Ets-1, which is mutated in the v-Ets oncoprotein, forms an alpha-helix that packs anti-parallel to the N-terminal helix of the ETS domain. In this position, the C-terminal helix is poised to interact directly with an N-terminal inhibitory region in Ets-1 as well as the wHTH Motif. This explains structurally the concerted role of residues flanking the ETS domain in the intramolecular inhibition of Ets-1 DNA Binding.

  • interaction of murine ets 1 with gga Binding sites establishes the ets domain as a new DNA Binding Motif
    Genes & Development, 1992
    Co-Authors: Julie Nye, Jeannine M Petersen, Cathy V Gunther, Matthew D Jonsen, Barbara J. Graves
    Abstract:

    The proto-oncogene ets-1 is the founding member of a new family of eukaryotic transcriptional regulators. Using deletion mutants of murine ets-1 cDNA expressed in Escherichia coli, we show that the DNA-Binding domain corresponds closely to the ETS domain, an 85-amino-acid region that is conserved among ets family members. To investigate the specificity of DNA Binding of the ETS domain, we mapped the DNA contacts of a monomeric Ets-1 fragment by chemical protection and interference assays. DNA backbone interactions span a 20-nucleotide region and are localized on one face of the helix. Close phosphate and base contacts are restricted to 10 central nucleotides. Contacts map to the major groove in the center of the site. Flanking minor groove interactions also are predicted. To determine the sequence preference in the close contact zone, we selected a pool of high-affinity Binding sites using a purified Ets-1 carboxy-terminal fragment. Our Ets-1-selected consensus, 5'-A/GCCGGAA/TGT/C-3', differs from the Binding consensus for the Drosophila ETS domain protein E74A, suggesting that specificity of action of ets family members is mediated by the ETS domain. Compared to other well-characterized classes of DNA-Binding proteins, Ets-1 produces a unique pattern of DNA contacts. These studies demonstrate that the ETS domain proteins bind DNA in a novel manner.

Lawrence P. Mcintosh - One of the best experts on this subject based on the ideXlab platform.

  • solution structure of the ets domain from murine ets 1 a winged helix turn helix DNA Binding Motif
    The EMBO Journal, 1996
    Co-Authors: Logan W Donaldson, Barbara J. Graves, Jeannine M Petersen, Lawrence P. Mcintosh
    Abstract:

    Ets-1 is the prototypic member of the ets family of transcription factors. This family is characterized by the conserved ETS domain that mediates specific DNA Binding. Using NMR methods, we have determined the structure of a fragment of murine Ets-1 composed of the 85 residue ETS domain and a 25 amino acid extension that ends at its native C-terminus. The ETS domain folds into a helix-turn-helix Motif on a four-stranded anti-parallel beta-sheet scaffold. This structure places Ets-1 in the winged helix-turn-helix (wHTH) family of DNA Binding proteins and provides a model for interpreting the sequence conservation of the ETS domain and the specific interaction of Ets-1 with DNA. The C-terminal sequence of Ets-1, which is mutated in the v-Ets oncoprotein, forms an alpha-helix that packs anti-parallel to the N-terminal helix of the ETS domain. In this position, the C-terminal helix is poised to interact directly with an N-terminal inhibitory region in Ets-1 as well as the wHTH Motif. This explains structurally the concerted role of residues flanking the ETS domain in the intramolecular inhibition of Ets-1 DNA Binding.

Chris P Ponting - One of the best experts on this subject based on the ideXlab platform.

  • The helix-hairpin-helix DNA-Binding Motif: a structural basis for non- sequence-specific recognition of DNA
    Nucleic Acids Res, 1996
    Co-Authors: A J Doherty, Louise C Serpell, Chris P Ponting
    Abstract:

    One, two or four copies of the 'helix-hairpin-helix' (HhH) DNA-Binding Motif are predicted to occur in 14 homologous families of proteins. The predicted DNA-Binding function of this Motif is shown to be consistent with the crystallographic structure of rat polymerase beta, complexed with DNA template-primer [Pelletier, H., Sawaya, M.R., Kumar, A., Wilson, S.H. and Kraut, J. (1994) Science 264, 1891-1903] and with biochemical data. Five crystal structures of predicted HhH Motifs are currently known: two from rat pol beta and one each in endonuclease III, AlkA and the 5' nuclease domain of Taq pol I. These Motifs are more structurally similar to each other than to any other structure in current databases, including helix-turn-helix Motifs. The clustering of the five HhH structures separately from other bi-helical structures in searches indicates that all members of the 14 families of proteins described herein possess similar HhH structures. By analogy with the rat pol beta structure, it is suggested that each of these HhH Motifs bind DNA in a non-sequence-specific manner, via the formation of hydrogen bonds between protein backbone nitrogens and DNA phosphate groups. This type of interaction contrasts with the sequence-specific interactions of other Motifs, including helix-turn-helix structures. Additional evidence is provided that alphaherpesvirus virion host shutoff proteins are members of the polymerase I 5'-nuclease and FEN1- like endonuclease gene family, and that a novel HhH-containing DNA- Binding domain occurs in the kinesin-like molecule nod, and in other proteins such as cnjB, emb-5 and SPT6.