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A Nucleosome Bridging Mechanism for Activation of a Maintenance DNA Methyltransferase.

Record Type:	Language materials, manuscript : Monograph/item
Title/Author:	A Nucleosome Bridging Mechanism for Activation of a Maintenance DNA Methyltransferase./
Author:	Stoddard, Caitlin I.
Description:	1 online resource (121 pages)
Notes:	Source: Dissertation Abstracts International, Volume: 79-09(E), Section: B.
Contained By:	Dissertation Abstracts International79-09B(E).
Subject:	Biochemistry. -
Online resource:	click for full text (PQDT)
ISBN:	9780355857603

A Nucleosome Bridging Mechanism for Activation of a Maintenance DNA Methyltransferase.
Stoddard, Caitlin I.

A Nucleosome Bridging Mechanism for Activation of a Maintenance DNA Methyltransferase. - 1 online resource (121 pages)

Source: Dissertation Abstracts International, Volume: 79-09(E), Section: B.

Thesis (Ph.D.)--University of California, San Francisco, 2018.

Includes bibliographical references

DNA methylation and histone H3 lysine 9 methylation (H3K9me) are hallmarks of heterochromatin in plants and mammals and are successfully maintained across generations. The biochemical and structural basis for this maintenance is poorly understood. The maintenance DNA methyltransferase from Zea mays, ZMET2, recognizes H3K9me2 via a chromodomain (CD) and bromo-adjacent homology domain (BAH), which flank the catalytic domain. Here, we show that the H3K9me mark allosterically stimulates ZMET2 activity and also substantially increases the specificity of ZMET2 for hemimethylated versus unmethylated DNA. Interestingly, dinucleosomes are the preferred ZMET2 substrate, with DNA methylation targeted primarily to linker DNA. Further, while the CD stabilizes ZMET2 binding, the BAH domain is critical for catalysis and serves as an allosteric regulator of the enzyme. Negative stain electron microscopy shows a single ZMET2 molecule bridging two nucleosomes within a dinucleosome, consistent with the biochemical analyses. We propose a model in which CD-mediated binding and allosteric activation via BAH/H3K9me interactions coupled with nucleosome bridging allows ZMET2 to correctly read the chromatin context and thereby faithfully maintain DNA methylation and reinforce heterochromatic elements across the genome.

Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2018

Mode of access: World Wide Web

ISBN: 9780355857603Subjects--Topical Terms:

582831
Biochemistry.
Index Terms--Genre/Form:

554714
Electronic books.

A Nucleosome Bridging Mechanism for Activation of a Maintenance DNA Methyltransferase.
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100 1 $a Stoddard, Caitlin I. $3 1193310
245 1 2 $a A Nucleosome Bridging Mechanism for Activation of a Maintenance DNA Methyltransferase.
264 0 $c 2018
300 $a 1 online resource (121 pages)
336 $a text $b txt $2 rdacontent
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500 $a Source: Dissertation Abstracts International, Volume: 79-09(E), Section: B.
500 $a Adviser: Geeta J. Narlikar.
502 $a Thesis (Ph.D.)--University of California, San Francisco, 2018.
504 $a Includes bibliographical references
520 $a DNA methylation and histone H3 lysine 9 methylation (H3K9me) are hallmarks of heterochromatin in plants and mammals and are successfully maintained across generations. The biochemical and structural basis for this maintenance is poorly understood. The maintenance DNA methyltransferase from Zea mays, ZMET2, recognizes H3K9me2 via a chromodomain (CD) and bromo-adjacent homology domain (BAH), which flank the catalytic domain. Here, we show that the H3K9me mark allosterically stimulates ZMET2 activity and also substantially increases the specificity of ZMET2 for hemimethylated versus unmethylated DNA. Interestingly, dinucleosomes are the preferred ZMET2 substrate, with DNA methylation targeted primarily to linker DNA. Further, while the CD stabilizes ZMET2 binding, the BAH domain is critical for catalysis and serves as an allosteric regulator of the enzyme. Negative stain electron microscopy shows a single ZMET2 molecule bridging two nucleosomes within a dinucleosome, consistent with the biochemical analyses. We propose a model in which CD-mediated binding and allosteric activation via BAH/H3K9me interactions coupled with nucleosome bridging allows ZMET2 to correctly read the chromatin context and thereby faithfully maintain DNA methylation and reinforce heterochromatic elements across the genome.
533 $a Electronic reproduction. $b Ann Arbor, Mich. : $c ProQuest, $d 2018
538 $a Mode of access: World Wide Web
650 4 $a Biochemistry. $3 582831
655 7 $a Electronic books. $2 local $3 554714
690 $a 0487
710 2 $a ProQuest Information and Learning Co. $3 1178819
710 2 $a University of California, San Francisco. $b Biochemistry and Molecular Biology. $3 1193311
773 0 $t Dissertation Abstracts International $g 79-09B(E).
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10745853 $z click for full text (PQDT)