Chromatin Structure and the Pioneering Transcription Factor FOXA1 Regulate TDG-Mediated Removal of 5-Formylcytosine from DNA
| Autor: | Charles E. Deckard, Jonathan T. Sczepanski, Deb Ranjan Banerjee |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Hepatocyte Nuclear Factor 3-alpha
Models Molecular Chemistry DNA General Chemistry 010402 general chemistry 01 natural sciences Biochemistry Chromatin Thymine DNA Glycosylase Catalysis 0104 chemical sciences Cell biology Cytosine chemistry.chemical_compound Colloid and Surface Chemistry DNA demethylation Higher Order Chromatin Structure Humans Nucleosome Thymine-DNA glycosylase Enhancer Transcription factor |
| Zdroj: | Journal of the American Chemical Society. 141:14110-14114 |
| ISSN: | 1520-5126 0002-7863 |
| Popis: | Although a functional relationship between active DNA demethylation and chromatin structure is often implied, direct experimental evidence is lacking. We investigated the relationship between chromatin structure and thymine DNA glycosylase (TDG) using chemically defined nucleosome arrays containing site-specifically positioned 5-formylcytosine (5fC) residues. We show that the extent of array compaction, as well as nucleosome positioning, dramatically influence the ability of TDG to excise 5fC from DNA, indicating that the chromatin structure is likely a key determinant of whether 5fC is removed from the genome or retained as an epigenetic mark. Furthermore, the H2A.Z/H3.3 double-variant nucleosome and the pioneering transcription factor forkhead box A1 (FOXA1), both of which are implicated in shaping the chromatin landscape during demethylation of tissue-specific enhancers, differentially regulate TDG activity on chromatin. Together, this work provides the first direct evidence that the higher order chromatin structure regulates active DNA demethylation through TDG and provides novel insights into the mechanism of 5fC turnover at enhancers. |
| Databáze: | OpenAIRE |
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