BANP opens chromatin and activates CpG-island-regulated genes
- 7 July 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature
- Vol. 596 (7870), 133-137
- https://doi.org/10.1038/s41586-021-03689-8
Abstract
The majority of gene transcripts generated by RNA polymerase II in mammalian genomes initiate at CpG island (CGI) promoters1,2, yet our understanding of their regulation remains limited. This is in part due to the incomplete information that we have on transcription factors, their DNA-binding motifs and which genomic binding sites are functional in any given cell type3,4,5. In addition, there are orphan motifs without known binders, such as the CGCG element, which is associated with highly expressed genes across human tissues and enriched near the transcription start site of a subset of CGI promoters6,7,8. Here we combine single-molecule footprinting with interaction proteomics to identify BTG3-associated nuclear protein (BANP) as the transcription factor that binds this element in the mouse and human genome. We show that BANP is a strong CGI activator that controls essential metabolic genes in pluripotent stem and terminally differentiated neuronal cells. BANP binding is repelled by DNA methylation of its motif in vitro and in vivo, which epigenetically restricts most binding to CGIs and accounts for differential binding at aberrantly methylated CGI promoters in cancer cells. Upon binding to an unmethylated motif, BANP opens chromatin and phases nucleosomes. These findings establish BANP as a critical activator of a set of essential genes and suggest a model in which the activity of CGI promoters relies on methylation-sensitive transcription factors that are capable of chromatin opening.Keywords
This publication has 89 references indexed in Scilit:
- An integrated encyclopedia of DNA elements in the human genomeNature, 2012
- DNA-binding factors shape the mouse methylome at distal regulatory regionsNature, 2011
- Genome-Wide Approaches to Determining Nucleosome Occupancy in Metazoans Using MNase-SeqPublished by Springer Science and Business Media LLC ,2011
- Simultaneous Single‐Molecule Mapping of Protein‐DNA Interactions and DNA Methylation by MAPitCurrent Protocols in Molecular Biology, 2011
- Reversed‐phase chromatography with multiple fraction concatenation strategy for proteome profiling of human MCF10A cellsProteomics, 2011
- Andromeda: A Peptide Search Engine Integrated into the MaxQuant EnvironmentJournal of Proteome Research, 2011
- Simple Combinations of Lineage-Determining Transcription Factors Prime cis-Regulatory Elements Required for Macrophage and B Cell IdentitiesMolecular Cell, 2010
- Lineage-Specific Polycomb Targets and De Novo DNA Methylation Define Restriction and Potential of Neuronal ProgenitorsMolecular Cell, 2008
- Distribution, silencing potential and evolutionary impact of promoter DNA methylation in the human genomeNature Genetics, 2007
- New DNA sequence rules for high affinity binding to histone octamer and sequence-directed nucleosome positioningJournal of Molecular Biology, 1998