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@ARTICLE{Ravichandran:491473,
author = {Ravichandran, Mirunalini and Rafalski, Dominik and Davies,
Claudia I. and Ortega-Recalde, Oscar and Nan, Xinsheng and
Glanfield, Cassandra R. and Kotter, Annika and Misztal,
Katarzyna and Wang, Andrew H. and Wojciechowski, Marek and
Rażew, Michał and Mayyas, Issam M. and Kardailsky, Olga
and Schwartz, Uwe and Zembrzycki, Krzysztof and Morison, Ian
M. and Helm, Mark and Weichenhan, Dieter and Jurkowska,
Renata Z. and Krueger, Felix and Plass, Christoph and
Zacharias, Martin and Bochtler, Matthias and Hore, Timothy
A. and Jurkowski, Tomasz P.},
title = {{P}ronounced sequence specificity of the {TET} enzyme
catalytic domain guides its cellular function},
journal = {Science advances},
volume = {8},
number = {36},
issn = {2375-2548},
address = {Washington, DC [u.a.]},
publisher = {Assoc.},
reportid = {PUBDB-2023-00182},
pages = {eabm2427},
year = {2022},
abstract = {TET (ten-eleven translocation) enzymes catalyze the
oxidation of 5-methylcytosine bases in DNA, thus driving
active and passive DNA demethylation. Here, we report that
the catalytic domain of mammalian TET enzymes favor CGs
embedded within basic helix-loop-helix and basic leucine
zipper domain transcription factor–binding sites, with up
to 250-fold preference in vitro. Crystal structures and
molecular dynamics calculations show that sequence
preference is caused by intrasubstrate interactions and CG
flanking sequence indirectly affecting enzyme conformation.
TET sequence preferences are physiologically relevant as
they explain the rates of DNA demethylation in TET-rescue
experiments in culture and in vivo within the zygote and
germ line. Most and least favorable TET motifs represent DNA
sites that are bound by methylation-sensitive
immediate-early transcription factors and octamer-binding
transcription factor 4 (OCT4), respectively, illuminating
TET function in transcriptional responses and pluripotency
support.},
cin = {DOOR ; HAS-User},
ddc = {500},
cid = {I:(DE-H253)HAS-User-20120731},
pnm = {6G3 - PETRA III (DESY) (POF4-6G3)},
pid = {G:(DE-HGF)POF4-6G3},
experiment = {EXP:(DE-H253)P-P11-20150101},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:36070377},
UT = {WOS:000911968500003},
doi = {10.1126/sciadv.abm2427},
url = {https://bib-pubdb1.desy.de/record/491473},
}