Site- and allele-specific de-silencing of polycomb repressive activity by insertional oncogenesis: a new recurrent mechanism of TAL1 activation in T-ALL

ABSTRACT: T-cell acute lymphoblastic leukemia’s (T-ALL) are malignant proliferations of thymocytes occurring through a large diversity of genomic and epigenetic alteration. TAL1 is amongst the most frequently deregulated oncogenes. Known TAL1 dysregulation mechanisms consist of t(1;14) translocations and SIL-TAL deletions. Yet, over half of TAL1+ cases lack TAL1 lesions, pointing to unrecognized (epi)genetic deregulation mechanisms. In such “unresolved cases”, TAL1 expression can be mono-allelic, compatible with a direct alteration in cis within or around the TAL1 gene, or bi-allelic, likely reflecting indirect deregulation in trans. Using ChIP-seq, we show that TAL1 is normally silenced in the T-cell lineage, and that the polycomb H3K27me3 repressive mark is focally diminished in TAL1+ T-ALLs. Seq

ORGANISM(S): Homo sapiens

SUBMITTER: Romain Fenouil 

PROVIDER: E-GEOD-59257 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress