Journal Article

PUBDB-2023-00182

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Pronounced sequence specificity of the TET enzyme catalytic domain guides its cellular function

Ravichandran, M. ; Rafalski, D. ; Davies, C. I. ; Ortega-Recalde, O. ; Nan, X. ; Glanfield, C. R. ; Kotter, A. ; Misztal, K. ; Wang, A. H. ; Wojciechowski, M.Extern*EMBL* ; Rażew, M. ; Mayyas, I. M. ; Kardailsky, O. ; Schwartz, U. ; Zembrzycki, K. ; Morison, I. M. ; Helm, M. ; Weichenhan, D. ; Jurkowska, R. Z. ; Krueger, F. ; Plass, C. ; Zacharias, M. ; Bochtler, M.Extern* ; Hore, T. A. (Corresponding author) ; Jurkowski, T. P. (Corresponding author)

2022
Assoc. Washington, DC [u.a.]

This record in other databases:        

Please use a persistent id in citations: doi:10.1126/sciadv.abm2427  doi:10.3204/PUBDB-2023-00182

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.

---

Contributing Institute(s):

1. DOOR-User (DOOR ; HAS-User)

Research Program(s):

1. 6G3 - PETRA III (DESY) (POF4-6G3) (POF4-6G3)

Experiment(s):

1. PETRA Beamline P11 (PETRA III)

Appears in the scientific report 2022

---

Database coverage:
; ; ; ; Article Processing Charges ; Clarivate Analytics Master Journal List ; Current Contents - Physical, Chemical and Earth Sciences ; DOAJ Seal ; Ebsco Academic Search ; Essential Science Indicators ; Fees ; IF >= 10 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection ; Zoological Record

---