GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE128818 Query DataSets for GSE128818
Status Public on May 07, 2020
Title Aberrant phase separation of transcription factors in human developmental disorders
Organisms Gallus gallus; Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Third-party reanalysis
Summary Components of the transcription machinery can undergo liquid-liquid phase separation, but the functional importance of phase-separated condensates in transcriptional control is not well understood. Here we report that disease-causing mutations in several transcription factors (TFs) alter the phase separation capacity of those TFs. We first demonstrate that the Hoxd13 TF, and its intrinsically disordered N-terminus form phase-separated condensates. Expansions of a polyalanine repeat, which cause hereditary synpolydactyly in humans, facilitate phase separation of Hoxd13, and alter the transcriptional program of several cell types in a cell-specific manner in vivo. Disease-associated expansions of aminoacid repeats in intrinsically disordered regions of other TFs were similarly found to alter phase separation. These results suggest that aberrant phase separation of transcriptional regulators may underlie a spectrum of human pathologies.

The paper is available at
Overall design Single-cell RNAseq data was performed on mouse limb buds from embyros at developmental stage E12.5 from a WT and a SPDH mutant condition. Samples from each condition were sequenced with the 10X Genomics singlecell RNA sequencing system. Further, we use H3K27ac and H3K27me3 ChIPseq to see if transcriptional changes are reflected in chromosome structure.
Reanalysis of Samples GSM3568504 and GSM3568505 (processed data file: H3K27Ac-L-E125-Wt-Mm_merged_8_peaks.bed ).
Third-party reanalysis of Samples GSM2151014 and GSM2151018 (processed data file: hoxd13_peaks_pv1e10_e11_5.bed). Data processing steps same as those for the other ChIP-seq samples in GSE128818.
Contributor(s) Mackowiak SD, Basu S, Asimi V, Grosswendt S, Sampath Kumar A, Knezevic D, Ibrahim DM, Niskanen H, Ali S, Mundlos S, Meissner A, Hnisz D
Citation(s) 32386547
Submission date Mar 25, 2019
Last update date Aug 24, 2020
Contact name Denes Hnisz
Organization name Max Planck Institute for Molecular Genetics
Department Genome Regulation
Lab Hnisz Lab
Street address Ihnestra├če 63-73
City Berlin
State/province Berlin
ZIP/Postal code 14195
Country Germany
Platforms (4)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
GPL19057 Illumina NextSeq 500 (Mus musculus)
GPL21103 Illumina HiSeq 4000 (Mus musculus)
Samples (19)
GSM3685917 WT_E12.5_scRNASeq
GSM3685918 SPDH_E12.5_scRNASeq
GSM3685919 SPDH_H3K27ac_ChIPSeq
Reanalysis of GSM2151014
Reanalysis of GSM2151018
BioProject PRJNA528953
SRA SRP189380

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE128818_H3K27Ac-L-E125-Wt-Mm_merged_8_peaks.bed.gz 189.7 Kb (ftp)(http) BED
GSE128818_H3K27me3-L-E125-Wt-Mm_merged_5_peaks.bed.gz 163.3 Kb (ftp)(http) BED
GSE128818_RAW.tar 96.7 Mb (http)(custom) TAR (of BED, MTX, TSV) 318.6 Mb (ftp)(http) BW 295.9 Mb (ftp)(http) BW
GSE128818_WT_chicken_peaks_merged.bed.gz 353.7 Kb (ftp)(http) BED
GSE128818_hoxd13_peaks_pv1e10_e11_5.bed.gz 266.9 Kb (ftp)(http) BED
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap