An all-to-all approach to the identification of sequence-specific readers for epigenetic DNA modifications on cytosine
| Autor: | Qifeng Song, Heng Zhu, Peng Jin, Jiang Qian, Cedric Moore, Guohua Wang, Hongjun Song, Ximei Luo, Jun Wan, Guang Song, Ying Cheng |
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| Rok vydání: | 2021 |
| Předmět: |
Epigenomics
0301 basic medicine Science Human Embryonic Stem Cells USF2 General Physics and Astronomy Computational biology Biology Article General Biochemistry Genetics and Molecular Biology Cell Line Epigenesis Genetic 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Transcription (biology) Consensus sequence Humans Epigenetics Author Correction Enhancer Gene Library 030304 developmental biology 0303 health sciences Multidisciplinary Assay systems High-throughput screening DNA General Chemistry Embryonic stem cell Recombinant Proteins Enhancer Elements Genetic 030104 developmental biology CpG site chemistry 5-Methylcytosine Screening Upstream Stimulatory Factors CpG Islands Epigenetics analysis Cytosine 030217 neurology & neurosurgery |
| Zdroj: | Nature Communications Nature Communications, Vol 12, Iss 1, Pp 1-16 (2021) |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-021-20950-w |
| Popis: | Epigenetic modifications of DNA play important roles in many biological processes. Identifying readers of these epigenetic marks is a critical step towards understanding the underlying mechanisms. Here, we present an all-to-all approach, dubbed digital affinity profiling via proximity ligation (DAPPL), to simultaneously profile human TF-DNA interactions using mixtures of random DNA libraries carrying different epigenetic modifications (i.e., 5-methylcytosine, 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine) on CpG dinucleotides. Many proteins that recognize consensus sequences carrying these modifications in symmetric and/or hemi-modified forms are identified. We further demonstrate that the modifications in different sequence contexts could either enhance or suppress TF binding activity. Moreover, many modifications can affect TF binding specificity. Furthermore, symmetric modifications show a stronger effect in either enhancing or suppressing TF-DNA interactions than hemi-modifications. Finally, in vivo evidence suggests that USF1 and USF2 might regulate transcription via hydroxymethylcytosine-binding activity in weak enhancers in human embryonic stem cells. Identifying readers of epigenetic marks is a critical step for understanding the role of epigenetic marks in biology. Here, the authors applied DAPPL, an all-to-all approach to profile the interactions between TFs and epigenetic modified DNA libraries. |
| Databáze: | OpenAIRE |
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