The HDAC7-TET2 epigenetic axis is essential during early B lymphocyte development [ATAC-seq]
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ABSTRACT: The establishment of proper epigenomic landscape is essential during B lymphocyte development in order to acquire a correct B cell identity at each cellular differentiation stage. We previously identified HDAC7 as a critical regulator of early B cell development. Its absence indeed led to the aberrant activation of inappropriate lineage genes, a reduction of proliferation and an increase in cell apoptosis. More recently, we have demonstrated that HDAC7 loss in infant pro-B-ALL associates with poor prognosis. Here we shed light into the HDAC7-mediated molecular mechanisms during early B cell development. HDAC7 deficiency drives not only the expression of inappropriate lineage genes, but also global chromatin de-condensation and deregulation of epigenetic regulators of DNA methylation and potential damaging elements. Specifically, HDAC7 absence induces the expression of TET2, which promotes DNA 5-hydroxymethylation and aberrant gene activation. HDAC7 deficiency also results in the uncontrolled expression of microRNAs and non-coding elements such as LINE-1 transposable elements. These findings are relevant for the mechanistic explanation of why HDAC7 is affected in multiple B-related hematological malignancies. Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) was performed in murine pro-B and pre-B lymphocytes.
ORGANISM(S): Mus musculus
PROVIDER: GSE204672 | GEO | 2022/06/27
REPOSITORIES: GEO
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