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Series GSE121066 Query DataSets for GSE121066
Status Public on Nov 13, 2018
Title Trisomy of a ‘Down syndrome critical region’ globally amplifies transcription via HMGN1 overexpression [proB RNA-Seq]
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Down 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 ERCC spike in RNA-Seq in mouse proB_Ts1Rhr cells
 
Contributor(s) Mowery CT, Lane AA
Citation(s) 30428356
Submission date Oct 10, 2018
Last update date Mar 25, 2019
Contact name James Bradner
E-mail(s) bradner_computation@dfci.harvard.edu
Organization name Dana-Farber Cancer Institute
Department Medical Oncology
Lab Bradner Lab
Street address 450 Brookline
City Boston
State/province MA
ZIP/Postal code 02215
Country USA
 
Platforms (1)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (9)
GSM3425402 PROB_HMGN1_4
GSM3425403 PROB_HMGN1_5
GSM3425404 PROB_HMGN1_6
This SubSeries is part of SuperSeries:
GSE121071 Trisomy of a ‘Down syndrome critical region’ globally amplifies transcription via HMGN1 overexpression
Relations
BioProject PRJNA495598
SRA SRP164925

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Supplementary file Size Download File type/resource
GSE121066_PROB_all_fpkm_exprs_norm.txt.gz 922.9 Kb (ftp)(http) TXT
GSE121066_PROB_all_fpkm_exprs_raw.txt.gz 558.7 Kb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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