Open AccessProteome‐Wide Profiling of Readers for DNA Modification
Author(s) -
Bai Lin,
Yang Guojian,
Qin Zhaoyu,
Lyu Jiacheng,
Wang Yunzhi,
Feng Jinwen,
Liu Mingwei,
Gong Tongqing,
Li Xianju,
Li Zhengyang,
Li Jixi,
Qin Jun,
Yang Wenjun,
Ding Chen
Publication year - 2021
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.202101426
Subject(s) - epigenetics , dna , biology , dna methylation , computational biology , epigenomics , transcription factor , genetics , 5 hydroxymethylcytosine , gene , microbiology and biotechnology , gene expression
DNA modifications, represented by 5‐methylcytosine (5mC), 5‐hydroxymethylcytosine (5hmC), 5‐formylcytosine (5fC), and 5‐carboxylcytosine (5caC), play important roles in epigenetic regulation of biological processes. The specific recognition of DNA modifications by the transcriptional protein machinery is thought to be a potential mechanism for epigenetic‐driven gene regulation, and many modified DNA‐specific binding proteins have been uncovered. However, the panoramic view of the roles of DNA modification readers at the proteome level remains largely unclear. Here, a recently developed concatenated tandem array of consensus transcription factor (TF) response elements (catTFREs) approach is employed to profile the binding activity of TFs at DNA modifications. Modified DNA‐binding activity is quantified for 1039 TFs, representing 70% of the TFs in the human genome. Additionally, the modified DNA‐binding activity of 600 TFs is monitored during the mouse brain development from the embryo to the adult stages. Readers of these DNA modifications are predicted, and the hierarchical networks between the transcriptional protein machinery and modified DNA are described. It is further demonstrated that ZNF24 and ZSCAN21 are potential readers of 5fC‐modified DNA. This study provides a landscape of TF–DNA modification interactions that can be used to elucidate the epigenetic‐related transcriptional regulation mechanisms under physiological conditions.