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  1. Article ; Online: Zinc Finger Readers of Methylated DNA.

    Hudson, Nicholas O / Buck-Koehntop, Bethany A

    Molecules (Basel, Switzerland)

    2018  Volume 23, Issue 10

    Abstract: DNA methylation is a prevalent epigenetic modification involved in regulating a number of essential cellular processes, including genomic accessibility and transcriptional outcomes. As such, aberrant alterations in global DNA methylation patterns have ... ...

    Abstract DNA methylation is a prevalent epigenetic modification involved in regulating a number of essential cellular processes, including genomic accessibility and transcriptional outcomes. As such, aberrant alterations in global DNA methylation patterns have been associated with a growing number of disease conditions. Nevertheless, the full mechanisms by which DNA methylation information is interpreted and translated into genomic responses is not yet fully understood. Methyl-CpG binding proteins (MBPs) function as important mediators of this essential process by selectively reading DNA methylation signals and translating this information into down-stream cellular outcomes. The Cys₂His₂ zinc finger scaffold is one of the most abundant DNA binding motifs found within human transcription factors, yet only a few zinc finger containing proteins capable of conferring selectivity for mCpG over CpG sites have been characterized. This review summarizes our current structural understanding for the mechanisms by which the zinc finger MBPs evaluated to date read this essential epigenetic mark. Further, some of the biological implications for mCpG readout elicited by this family of MBPs are discussed.
    MeSH term(s) CpG Islands/genetics ; DNA Methylation/genetics ; DNA-Binding Proteins/chemistry ; DNA-Binding Proteins/genetics ; Epigenesis, Genetic ; Humans ; Signal Transduction ; Transcription Factors/chemistry ; Transcription Factors/genetics ; Zinc Fingers/genetics
    Chemical Substances DNA-Binding Proteins ; Transcription Factors
    Language English
    Publishing date 2018-10-07
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 1413402-0
    ISSN 1420-3049 ; 1431-5165 ; 1420-3049
    ISSN (online) 1420-3049
    ISSN 1431-5165 ; 1420-3049
    DOI 10.3390/molecules23102555
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.MO 81: Show issues

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  2. Article ; Online: Cys

    Hodges, Amelia J / Hudson, Nicholas O / Buck-Koehntop, Bethany A

    Journal of molecular biology

    2019  Volume 432, Issue 6, Page(s) 1640–1660

    Abstract: DNA methylation is an essential epigenetic modification involved in the maintenance of genomic stability, preservation of cellular identity, and regulation of the transcriptional landscape needed to maintain cellular function. In an increasing number of ... ...

    Abstract DNA methylation is an essential epigenetic modification involved in the maintenance of genomic stability, preservation of cellular identity, and regulation of the transcriptional landscape needed to maintain cellular function. In an increasing number of disease conditions, DNA methylation patterns are inappropriately distributed in a manner that supports the disease phenotype. Methyl-CpG binding proteins (MBPs) are specialized transcription factors that read and translate methylated DNA signals into recruitment of protein assemblies that can alter local chromatin architecture and transcription. MBPs thus play a key intermediary role in gene regulation for both normal and diseased cells. Here, we highlight established and potential structure-function relationships for the best characterized members of the zinc finger (ZF) family of MBPs in propagating DNA methylation signals into downstream cellular responses. Current and future investigations aimed toward expanding our understanding of ZF MBP cellular roles will provide needed mechanistic insight into normal and disease state functions, as well as afford evaluation for the potential of these proteins as epigenetic-based therapeutic targets.
    Language English
    Publishing date 2019-10-16
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 80229-3
    ISSN 1089-8638 ; 0022-2836
    ISSN (online) 1089-8638
    ISSN 0022-2836
    DOI 10.1016/j.jmb.2019.09.012
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 867: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  3. Article ; Online: Structural insights into methylated DNA recognition by the C-terminal zinc fingers of the DNA reader protein ZBTB38.

    Hudson, Nicholas O / Whitby, Frank G / Buck-Koehntop, Bethany A

    The Journal of biological chemistry

    2018  Volume 293, Issue 51, Page(s) 19835–19843

    Abstract: Methyl-CpG-binding proteins (MBPs) are selective readers of DNA methylation that play an essential role in mediating cellular transcription processes in both normal and diseased cells. This physiological function of MBPs has generated significant ... ...

    Abstract Methyl-CpG-binding proteins (MBPs) are selective readers of DNA methylation that play an essential role in mediating cellular transcription processes in both normal and diseased cells. This physiological function of MBPs has generated significant interest in understanding the mechanisms by which these proteins read and interpret DNA methylation signals. Zinc finger and BTB domain-containing 38 (ZBTB38) represents one member of the zinc finger (ZF) family of MBPs. We recently demonstrated that the C-terminal ZFs of ZBTB38 exhibit methyl-selective DNA binding within the ((A/G)TmCG(G/A)(mC/T)(G/A)) context both
    MeSH term(s) Amino Acid Sequence ; DNA/chemistry ; DNA/genetics ; DNA/metabolism ; DNA Contamination ; DNA Methylation ; Humans ; Models, Molecular ; Protein Binding ; Repressor Proteins/chemistry ; Repressor Proteins/metabolism ; Zinc Fingers
    Chemical Substances Repressor Proteins ; ZBTB38 protein, human ; DNA (9007-49-2)
    Language English
    Publishing date 2018-10-24
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1074/jbc.RA118.005147
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Uc I Zs.108: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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  4. Article ; Online: The C-Terminal Zinc Fingers of ZBTB38 are Novel Selective Readers of DNA Methylation.

    Pozner, Amir / Hudson, Nicholas O / Trewhella, Jill / Terooatea, Tommy W / Miller, Sven A / Buck-Koehntop, Bethany A

    Journal of molecular biology

    2017  Volume 430, Issue 3, Page(s) 258–271

    Abstract: Methyl-CpG binding proteins play an essential role in translating DNA methylation marks into a downstream transcriptional response, which has implications for both normal cell function as well as disease. Although for many of these proteins, a detailed ... ...

    Abstract Methyl-CpG binding proteins play an essential role in translating DNA methylation marks into a downstream transcriptional response, which has implications for both normal cell function as well as disease. Although for many of these proteins, a detailed mechanistic understanding for how this cellular process is mediated remains to be determined. ZBTB38 is an under-characterized member of the zinc finger (ZF) family of methyl-CpG binding proteins. Functional knowledge has been gained for its conserved methylated DNA binding N-terminal ZF region; however, a specific role for the C-terminal set of five ZFs remains to be elucidated. Here we demonstrate for the first time that a subset of the C-terminal ZBTB38 ZFs exhibit high-affinity DNA interactions and that preferential targeting of the consensus DNA site is methyl specific. Utilizing a hybrid approach, a model for the C-terminal ZBTB38 ZFs in complex with its cognate DNA target is proposed, providing insight into a possible novel mode of methylated DNA recognition. Furthermore, it is shown that the C-terminal ZFs of ZBTB38 can directly occupy promoters harboring the newly identified sequence motif in cell in a methyl-dependent manner and, depending on the gene context, contribute to modulating transcriptional response. Combined, these findings provide evidence for a key and novel physiological function for the C-terminal ZF domain of ZBTB38.
    MeSH term(s) Amino Acid Sequence ; CpG Islands ; DNA/chemistry ; DNA/metabolism ; DNA Methylation ; Humans ; Molecular Docking Simulation ; Protein Binding ; Repressor Proteins/chemistry ; Repressor Proteins/metabolism ; Zinc Fingers
    Chemical Substances Repressor Proteins ; ZBTB38 protein, human ; DNA (9007-49-2)
    Language English
    Publishing date 2017-12-27
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80229-3
    ISSN 1089-8638 ; 0022-2836
    ISSN (online) 1089-8638
    ISSN 0022-2836
    DOI 10.1016/j.jmb.2017.12.014
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 867: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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