AI Article Synopsis
- Researchers studied active enhancer elements identified by open chromatin and H3K27 acetylation (H3K27ac), but the role of enhancers without H3K27ac remains unclear.
- They discovered a new type of enhancer, called 'macro-Bound Enhancers,' marked by macroH2A variants, which seem to control enhancer activity even when H3K27ac isn't present.
- In breast cancer, reactivating these macro-bound enhancers is linked to cancer growth, while a deficiency in macroH2A enhances stem cell activity in normal mammary cells, suggesting a complex role in cell identity and cancer development.
Article Abstract
Considerable efforts have been made to characterize active enhancer elements, which can be annotated by accessible chromatin and H3 lysine 27 acetylation (H3K27ac). However, apart from poised enhancers that are observed in early stages of development and putative silencers, the functional significance of cis-regulatory elements lacking H3K27ac is poorly understood. Here we show that macroH2A histone variants mark a subset of enhancers in normal and cancer cells, which we coined 'macro-Bound Enhancers', that modulate enhancer activity. We find macroH2A variants localized at enhancer elements that are devoid of H3K27ac in a cell type-specific manner, indicating a role for macroH2A at inactive enhancers to maintain cell identity. In following, reactivation of macro-bound enhancers is associated with oncogenic programs in breast cancer and their repressive role is correlated with the activity of macroH2A2 as a negative regulator of BRD4 chromatin occupancy. Finally, through single cell epigenomic profiling of normal mammary stem cells derived from mice, we show that macroH2A deficiency facilitates increased activity of transcription factors associated with stem cell activity.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9950461 | PMC |
| http://dx.doi.org/10.1038/s42003-023-04571-1 | DOI Listing |
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