GSE121062 Trisomy of a ‘Down syndrome critical region’ globally amplifies transcription via HMGN1 overexpression [ChIP-Seq]

Contributors : Cody T Mowery ; Andrew A LaneSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Homo sapiensDown syndrome (DS, trisomy 21) is associated with developmental abnormalities and increased leukemia risk. To reconcile chromatin alterations with transcriptome changes in cells with trisomy 21, we performed paired exogenous spike-in normalized RNA and chromatin immunoprecipitation sequencing in DS models. Absolute per cell normalization unmasked global amplification of gene expression associated with trisomy 21. Overexpression of the nucleosome binding protein HMGN1 (encoded on chr21q22) recapitulated the transcriptional changes seen with triplication of a “Down syndrome critical region” on distal chromosome 21. Absolute exogenous normalized ChIP-seq (ChIP-Rx) also revealed a global increase in histone 3 lysine 27 acetylation caused by HMGN1. Genes most amplified downstream of HMGN1 were enriched for tumor- and developmental stage-specific program s of B-cell acute lymphoblastic leukemia dependent on the cellular context. These data offer a mechanistic explanation for DS transcriptional patterns, and suggest that further study of HMGN1 and RNA amplification in diverse DS phenotypes is warranted.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Genome binding/occupancy profiling by high throughput sequencing Homo sapiens Source Type: research