Flanking sequences influence the activity of TET1 and TET2 methylcytosine dioxygenases and affect genomic 5hmC patterns

被引：20

作者：

Adam, Sabrina ^{[1
]}

Bracker, Julia ^{[2
]}

Klingel, Viviane ^{[3
]}

Osteresch, Bernd ^{[2
]}

Radde, Nicole E. ^{[3
]}

Brockmeyer, Jens ^{[2
]}

Bashtrykov, Pavel ^{[1
]}

Jeltsch, Albert ^{[1
]}

机构：

[1] Univ Stuttgart, Inst Biochem & Tech Biochem, Dept Biochem, Allmandring 31, D-70569 Stuttgart, Germany

[2] Univ Stuttgart, Dept Food Chem, Inst Biochem & Tech Biochem, Allmandring 5b, D-70569 Stuttgart, Germany

[3] Univ Stuttgart, Inst Syst Theory & Automat Control, Pfaffenwaldring 9, D-70569 Stuttgart, Germany

来源：

COMMUNICATIONS BIOLOGY | 2022年 / 5卷 / 01期

关键词：

DNA DEMETHYLATION; STRUCTURAL BASIS; 5-METHYLCYTOSINE; 5-HYDROXYMETHYLCYTOSINE; METHYLATION; CPG; CONVERSION; MECHANISM; PROTEINS; EXCISION;

D O I：

10.1038/s42003-022-03033-4

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

TET dioxygenases convert 5-methylcytosine (5mC) preferentially in a CpG context into 5-hydroxymethylcytosine (5hmC) and higher oxidized forms, thereby initiating DNA demethylation, but details regarding the effects of the DNA sequences flanking the target 5mC site on TET activity are unknown. We investigated oxidation of libraries of DNA substrates containing one 5mC or 5hmC residue in randomized sequence context using single molecule readout of oxidation activity and sequence and show pronounced 20 and 70-fold flanking sequence effects on the catalytic activities of TET1 and TET2, respectively. Flanking sequence preferences were similar for TET1 and TET2 and also for 5mC and 5hmC substrates. Enhanced flanking sequence preferences were observed at non-CpG sites together with profound effects of flanking sequences on the specificity of TET2. TET flanking sequence preferences are reflected in genome-wide and local patterns of 5hmC and DNA demethylation in human and mouse cells indicating that they influence genomic DNA modification patterns in combination with locus specific targeting of TET enzymes.

引用

页数：13

共 53 条

[1] DNA sequence-dependent activity and base flipping mechanisms of DNMT1 regulate genome-wide DNA methylation [J].

Adam, Sabrina ;

Anteneh, Hiwot ;

Hornisch, Maximilian ;

Wagner, Vincent ;

Lu, Jiuwei ;

Radde, Nicole E. ;

Bashtrykov, Pavel ;

Song, Jikui ;

Jeltsch, Albert .

NATURE COMMUNICATIONS, 2020, 11 (01)

[2] The Galaxy platform for accessible, reproducible and collaborative biomedical analyses: 2018 update [J].

Afgan, Enis ;

Baker, Dannon ;

Batut, Berenice ;

van den Beek, Marius ;

Bouvier, Dave ;

Cech, Martin ;

Chilton, John ;

Clements, Dave ;

Coraor, Nate ;

Gruening, Bjoern A. ;

Guerler, Aysam ;

Hillman-Jackson, Jennifer ;

Hiltemann, Saskia ;

Jalili, Vahid ;

Rasche, Helena ;

Soranzo, Nicola ;

Goecks, Jeremy ;

Taylor, James ;

Nekrutenko, Anton ;

Blankenberg, Daniel .

NUCLEIC ACIDS RESEARCH, 2018, 46 (W1) :W537-W544

[3] Dynamics and Context-Dependent Roles of DNA Methylation [J].

Ambrosi, Christina ;

Manzo, Massimiliano ;

Baubec, Tuncay .

JOURNAL OF MOLECULAR BIOLOGY, 2017, 429 (10) :1459-1475

[4]

Bachman M, 2014, NAT CHEM, V6, P1049, DOI [10.1038/NCHEM.2064, 10.1038/nchem.2064]

[5] Manipulation of FASTQ data with Galaxy [J].

Blankenberg, Daniel ;

Gordon, Assaf ;

Von Kuster, Gregory ;

Coraor, Nathan ;

Taylor, James ;

Nekrutenko, Anton .

BIOINFORMATICS, 2010, 26 (14) :1783-1785

[6] Oxidative bisulfite sequencing of 5-methylcytosine and 5-hydroxymethylcytosine [J].

Booth, Michael J. ;

Ost, Tobias W. B. ;

Beraldi, Dario ;

Bell, Neil M. ;

Branco, Miguel R. ;

Reik, Wolf ;

Balasubramanian, Shankar .

NATURE PROTOCOLS, 2013, 8 (10) :1841-1851

[7] Non-canonical Bases in the Genome: The Regulatory Information Layer in DNA [J].

Carell, Thomas ;

Kurz, Matthias Q. ;

Mueller, Markus ;

Rossa, Martin ;

Spada, Fabio .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2018, 57 (16) :4296-4312

[8] Programming of DNA Methylation Patterns [J].

Cedar, Howard ;

Bergman, Yehudit .

ANNUAL REVIEW OF BIOCHEMISTRY, VOL 81, 2012, 81 :97-117

[9] Global delay in nascent strand DNA methylation [J].

Charlton, Jocelyn ;

Downing, Timothy L. ;

Smith, Zachary D. ;

Gu, Hongcang ;

Clement, Kendell ;

Pop, Ramona ;

Akopian, Veronika ;

Klages, Sven ;

Santos, David P. ;

Tsankov, Alexander M. ;

Timmermann, Bernd ;

Ziller, Michael J. ;

Kiskinis, Evangelos ;

Gnirke, Andreas ;

Meissner, Alexander .

NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2018, 25 (04) :327-+

[10] Tet2 Catalyzes Stepwise 5-Methylcytosine Oxidation by an Iterative and de novo Mechanism [J].

Crawford, Daniel J. ;

Liu, Monica Yun ;

Nabel, Christopher S. ;

Cao, Xing-Jun ;

Garcia, Benjamin A. ;

Kohli, Rahul M. .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2016, 138 (03) :730-733

← 1 2 3 4 5 6 →