10月表观遗传学研究最新资讯

       L1-associated genomic regions are deleted in somatic cells of the healthy human brain

Long interspersed element-1 (LINE-1 or L1) retrotransposition is known to create mosaicism by inserting L1 sequences into new locations of somatic cell genomes. In the current study, Erwin and collaborators examine the contribution of L1 in the somatic variation of healthy human brains. Using a novel protocol for single cell sequencing (SLAV-seq), they discovered that somatic L1-associated variants (SLAVs) are composed of two classes: L1 retrotransposition insertions and retrotransposition-independent L1-associated variants and are present in region of important neuronal genes such as DLG2.

Erwin, JA. et al: Nat Neurosci.. 2016 Sep 12. doi: 10.1038/nn.4388.

       Helicase Lymphoid-Specific Enzyme Contributes to the Maintenance of Methylation of SST1 Pericentromeric Repeats That Are Frequently Demethylated in Colon Cancer and Associate with Genomic Damage

In this current study Samuelsson and collaborators from the Manuel Perucho lab investigate the epigenetic landscape of a pericentromeric repeat called SST1. SST1 somatic demethylation is often associated with genome damage, especially in tumors with wild-type TP53. Using the Active Motif FFPE ChIP kit, the authors validated the change from high levels of DNA methylation and H3K9me3 at SST1 in normal tissues to a reduction of H3K9me3 and enrichment of H3K27me3 in tumors exhibiting SST1 demethylation. Moreover, they revealed with in vivo experiments the contribution of the helicase lymphoid-specific (HELLS) enzyme in SST1 methylation status and in genomic stability. Samuelsson, J.K. et al: Epigenomes 2016, 1(1), 2; doi:10.3390/epigenomes1010002

      Inheritable Silencing of Endogenous Genes by Hit-and-Run Targeted Epigenetic Editing

Using gene editing technology based on CRISPR-Cas9, scientists from the Lombardo lab have obtained inheritable silencing in different cell types, including primary T lymphocytes. By utilizing embryonic stem cells along with combinations of engineered transcriptional repressors that bind to and synergize at the target locus to instruct repressive histone marks and de novo DNA methylation, the authors were able to achieve long term memory of the repressive marks, opening new methods for targeted epigenome editing in medical applications.

Amabile, A. et al: Cell. 2016 Sep 22;167(1):219-232.e14 DOI: http://dx.doi.org/10.1016/j.cell.2016.09.006