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Trisomy of a ‘Down syndrome critical region’ globally amplifies transcription via HMGN1 overexpression

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE121071 | GEO | 2018/11/13

REPOSITORIES: GEO

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Trisomy of a Down Syndrome Critical Region Globally Amplifies Transcription via HMGN1 Overexpression.

Project description:Down syndrome (DS, trisomy 21) is associated with developmental abnormalities and increased leukemia risk. To reconcile chromatin alterations with transcriptome changes, we performed paired exogenous spike-in normalized RNA and chromatin immunoprecipitation sequencing in DS models. Absolute normalization unmasks global amplification of gene expression associated with trisomy 21. Overexpression of the nucleosome binding protein HMGN1 (encoded on chr21q22) recapitulates transcriptional changes seen with triplication of a Down syndrome critical region on distal chromosome 21, and HMGN1 is necessary for B cell phenotypes in DS models. Absolute exogenous-normalized chromatin immunoprecipitation sequencing (ChIP-Rx) also reveals a global increase in histone H3K27 acetylation caused by HMGN1. Transcriptional amplification downstream of HMGN1 is enriched for stage-specific programs of B cells and B cell acute lymphoblastic leukemia, dependent on the developmental 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.

| S-EPMC6321629 | biostudies-literature

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

Project description: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.

2018-11-13 | GSE121070 | GEO

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

Project description: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.

2018-11-13 | GSE121062 | GEO

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

Project description: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.

2018-11-13 | GSE121066 | GEO

Trisomy of a ‘Down syndrome critical region’ globally amplifies transcription via HMGN1 overexpression [NALM6 RNA-Seq]

Project description: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.

2018-11-13 | GSE121065 | GEO

Trisomy of a ‘Down syndrome critical region’ globally amplifies transcription via HMGN1 overexpression

Project description:Trisomy of a ‘Down syndrome critical region’ globally amplifies transcription via HMGN1 overexpression

| PRJNA495595 | ENA

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

Project description:Trisomy of a ‘Down syndrome critical region’ globally amplifies transcription via HMGN1 overexpression [SLAM-Seq]

| PRJNA495599 | ENA

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

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

| PRJNA495596 | ENA

Trisomy of a ‘Down syndrome critical region’ globally amplifies transcription via HMGN1 overexpression [NALM6 RNA-Seq]

Project description:Trisomy of a ‘Down syndrome critical region’ globally amplifies transcription via HMGN1 overexpression [NALM6 RNA-Seq]

| PRJNA495597 | ENA

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

Project description:Trisomy of a ‘Down syndrome critical region’ globally amplifies transcription via HMGN1 overexpression [proB RNA-Seq]

| PRJNA495598 | ENA

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