| Structural highlights
Function
DPF3_HUMAN Belongs to the neuron-specific chromatin remodeling complex (nBAF complex). During neural development a switch from a stem/progenitor to a post-mitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to post-mitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth (By similarity). Muscle-specific component of the BAF complex, a multiprotein complex involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Specifically binds acetylated lysines on histone 3 and 4 (H3K14ac, H3K9ac, H4K5ac, H4K8ac, H4K12ac, H4K16ac). In the complex, it acts as a tissue-specific anchor between histone acetylations and methylations and chromatin remodeling. It thereby probably plays an essential role in heart and skeletal muscle development.[1]
Publication Abstract from PubMed
Enhancers act to regulate cell-type-specific gene expression by facilitating the transcription of target genes. In mammalian cells, active or primed enhancers are commonly marked by monomethylation of histone H3 at lysine 4 (H3K4me1) in a cell-type-specific manner. Whether and how this histone modification regulates enhancer-dependent transcription programs in mammals is unclear. In this study, we conducted SILAC mass spectrometry experiments with mononucleosomes and identified multiple H3K4me1-associated proteins, including many involved in chromatin remodeling. We demonstrate that H3K4me1 augments association of the chromatin-remodeling complex BAF to enhancers in vivo and that, in vitro, H3K4me1-marked nucleosomes are more efficiently remodeled by the BAF complex. Crystal structures of the BAF component BAF45C indicate that monomethylation, but not trimethylation, is accommodated by BAF45C's H3K4-binding site. Our results suggest that H3K4me1 has an active role at enhancers by facilitating binding of the BAF complex and possibly other chromatin regulators.
Identification of H3K4me1-associated proteins at mammalian enhancers.,Local A, Huang H, Albuquerque CP, Singh N, Lee AY, Wang W, Wang C, Hsia JE, Shiau AK, Ge K, Corbett KD, Wang D, Zhou H, Ren B Nat Genet. 2018 Jan;50(1):73-82. doi: 10.1038/s41588-017-0015-6. Epub 2017 Dec, 18. PMID:29255264[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lange M, Kaynak B, Forster UB, Tonjes M, Fischer JJ, Grimm C, Schlesinger J, Just S, Dunkel I, Krueger T, Mebus S, Lehrach H, Lurz R, Gobom J, Rottbauer W, Abdelilah-Seyfried S, Sperling S. Regulation of muscle development by DPF3, a novel histone acetylation and methylation reader of the BAF chromatin remodeling complex. Genes Dev. 2008 Sep 1;22(17):2370-84. PMID:18765789 doi:22/17/2370
- ↑ Local A, Huang H, Albuquerque CP, Singh N, Lee AY, Wang W, Wang C, Hsia JE, Shiau AK, Ge K, Corbett KD, Wang D, Zhou H, Ren B. Identification of H3K4me1-associated proteins at mammalian enhancers. Nat Genet. 2018 Jan;50(1):73-82. doi: 10.1038/s41588-017-0015-6. Epub 2017 Dec, 18. PMID:29255264 doi:http://dx.doi.org/10.1038/s41588-017-0015-6
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