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Publication : A versatile mouse model of epitope-tagged histone H3.3 to study epigenome dynamics.

First Author  Bachu M Year  2019
Journal  J Biol Chem Volume  294
Issue  6 Pages  1904-1914
PubMed ID  30552116 Mgi Jnum  J:275341
Mgi Id  MGI:6304680 Doi  10.1074/jbc.RA118.005550
Citation  Bachu M, et al. (2019) A versatile mouse model of epitope-tagged histone H3.3 to study epigenome dynamics. J Biol Chem 294(6):1904-1914
abstractText  The variant histone H3.3 is incorporated into the genome in a transcription-dependent manner. This histone is thus thought to play a role in epigenetic regulation. However, our understanding of how H3.3 controls gene expression and epigenome landscape has remained incomplete. This is partly because precise localization of H3.3 in the genome has been difficult to decipher particularly for cells in vivo To circumvent this difficulty, we generated knockin mice, by homologous recombination, to replace both of the two H3.3 loci (H3f3a and H3f3b) with the hemagglutinin-tagged H3.3 cDNA cassette, which also contained a GFP gene. We show here that the hemagglutinin-tagged H3.3 and GFP are expressed in the majority of cells in all adult tissues tested. ChIP-seq data, combined with RNA-seq, revealed a striking correlation between the level of transcripts and that of H3.3 accumulation in expressed genes. Finally, we demonstrate that H3.3 deposition is markedly enhanced upon stimulation by interferon on interferon-stimulated genes, highlighting transcription-coupled H3.3 dynamics. Together, these H3.3 knockin mice serve as a useful experimental model to study epigenome regulation in development and in various adult cells in vivo.
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