Stabilization of Foxp3 expression by CRISPR-dCas9-based epigenome editing in mouse primary T cells

Epigenetics & Chromatin
Masahiro OkadaAkihiko Yoshimura

Abstract

Epigenome editing is expected to manipulate transcription and cell fates and to elucidate the gene expression mechanisms in various cell types. For functional epigenome editing, assessing the chromatin context-dependent activity of artificial epigenetic modifier is required. In this study, we applied clustered regularly interspaced short palindromic repeats (CRISPR)-dCas9-based epigenome editing to mouse primary T cells, focusing on theForkhead box P3 (Foxp3)gene locus, a master transcription factor of regulatory T cells (Tregs). TheFoxp3gene locus is regulated by combinatorial epigenetic modifications, which determine the Foxp3 expression. Foxp3 expression is unstable in transforming growth factor beta (TGF-β)-induced Tregs (iTregs), while stable in thymus-derived Tregs (tTregs). To stabilize Foxp3 expression in iTregs, we introduced dCas9-TET1CD (dCas9 fused to the catalytic domain (CD) of ten-eleven translocation dioxygenase 1 (TET1), methylcytosine dioxygenase) and dCas9-p300CD (dCas9 fused to the CD of p300, histone acetyltransferase) with guide RNAs (gRNAs) targeted to theFoxp3gene locus. Although dCas9-TET1CD induced partial demethylation in enhancer region called conserved non-coding DNA sequences 2 (CNS2), robust Foxp3...Continue Reading

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Methods Mentioned

BETA
acetylation
histone acetylation
flow cytometry
transfection
immunoprecipitation
electrophoresis
PCR
peptide array

Software Mentioned

CCTop

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