The androgen receptor (AR), a nuclear transcription factor (TF), is consistently reprogrammed during prostate tumorigenesis Overall design: Gene expresion profiles when LHSAR with overexpressed FOXA1, HOXB13 or FOXA1 and HOXB13 together compared with LacZ control
The androgen receptor cistrome is extensively reprogrammed in human prostate tumorigenesis.
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View SamplesDown 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 programs 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. Overall design: SLAM-seq in NALM6 human pre-B cells with engineered HMGN1 overexpression
Trisomy of a Down Syndrome Critical Region Globally Amplifies Transcription via HMGN1 Overexpression.
Cell line, Treatment, Subject
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