Table 2 HMGN1 and DS
From: Shaking up the silence: consequences of HMGN1 antagonizing PRC2 in the Down syndrome brain
DS Phenotype | Title | Related findings | References |
|---|---|---|---|
Overexpression of HMGN1 | Chromosomal protein HMG-14 gene maps to the Down syndrome region of human chromosome 21 and is overexpressed in mouse trisomy 16 | Ts16 mouse model of DS has 1.5 times more HMGN1 protein and mRNA than WT and supports the gene dosage effect of HMGN1 triplication | Pash et al. [192] |
| Â | Chromosomal protein HMG-14 is overexpressed in Down syndrome | Fibroblasts from DS individuals express HMGN1 at levels 1.6 higher than non-DS individuals | Pash et al. [193] |
| Â | Functional transcriptome analysis of the postnatal brain of the Ts1Cje mouse model for Down syndrome reveals global disruption of interferon-related molecular networks | HMGN1 is upregulated in the Ts1Cje mouse model of DS | Ling et al. [194] |
| Â | Transcriptional disruptions in Down syndrome: a case study in the Ts1Cje mouse cerebellum during post-natal development | HMGN1 was overexpressed in the cerebellum of the Ts1Cje mouse model of DS during post-natal development | Potier et al. [195] |
| Â | Bioinformatics analysis of biomarkers and transcriptional factor motifs in Down syndrome | Raw gene expression data from DS rat brain tissue, Ts1Cje cerebellum tissue, and adult human DS tissue analyzed using Gene Expression Omnibus and showed overexpression of HMGN1 | Kong et al. [201] |
| Â | Down syndrome developmental brain transcriptome reveals defective oligodendrocyte differentiation and myelination | Raw gene expression data analyzed in humans with DS using Gene Expression Omnibus and found HMGN1 overexpressed in the hippocampus, cerebellar cortex, and areas of the pre-frontal cortex, primary visual cortex, | Rodriguez-Ortiz et al. [203] |
Intellectual disability | Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium | A genome-wide association study of general cognitive function in adults found HMGN1 as the single gene-based significant association in the study | Davies et al. [288] |
Cancer | Triplication of a 21q22 region contributes to B cell transformation through HMGN1 overexpression and loss of histone H3 Lys27 trimethylation | HMGN1 suppresses H3K27me3 and promotes B cell proliferation in B-ALL | Lane et al. [171] |
Trisomy of a down syndrome critical region globally amplifies transcription via HMGN1 overexpression | HMGN1 globally amplifies transcription | Mowery et al. [174] | |
HMGN1 plays a significant role in CRLF2-driven Down Syndrome leukemia and provides a potential therapeutic target in this high-risk cohort | HMGN1 is involved in signaling pathways in CRLF2-driven DS leukemia | Page et al. [175] | |
Behavioral changes | The chromatin-binding protein HMGN1 regulates the expression of methyl CpG-binding protein 2 (MECP2) and affects the behavior of mice | HMGN1 downregulates MeCP2 and its aberrant expression produces behavioral changes in mice consistent with ASD and DS phenotypes | Abuhatzira et al. [180] |