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Series GSE155254 Query DataSets for GSE155254
Status Public on Dec 31, 2021
Title A Congenital Anemia Dissociates the Pleiotropic Functions of Master Transcription Factor GATA1 [Patient scRNA-seq]
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Master regulators, such as the hematopoietic transcription factor (TF) GATA1, play an essential role in orchestrating lineage commitment and differentiation1. However, the precise mechanisms by which such TFs regulate transcription through interactions with specific cis-regulatory elements remain incompletely understood2,3. Here, we characterize a distinct form of congenital hemolytic anemia caused by missense mutations in an intrinsically disordered region of GATA1, with a poorly understood role in transcriptional regulation. Through integrative functional approaches, we demonstrate that these mutations perturb GATA1 transcriptional activity by partially impairing nuclear localization and selectively altering precise chromatin occupancy by GATA1. These alterations in chromatin occupancy and concordant accessibility changes alter faithful gene expression, with failure to both effectively silence and activate select genes necessary for effective red cell production. We demonstrate how disease-causing mutations can reveal regulatory mechanisms that enable the faithful genomic targeting of master TFs during cellular differentiation.
 
Overall design In vitro cultured human bone marrow mononuclear cells from a patient carrying the GATA1 p.R307C mutation and healthy controls cells were sorted and forwarded to 10x scRNA-seq
 
Contributor(s) Ludwig L, Lareau C
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Submission date Jul 28, 2020
Last update date Jan 01, 2022
Contact name Caleb Lareau
E-mail(s) lareauc@mskcc.org
Organization name Memorial Sloan Kettering
Street address 417 E 68th St, Zuckerman - ZRC 1132
City New York
State/province New York
ZIP/Postal code 10065
Country USA
 
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (2)
GSM4698215 Patient-Control_scRNAseq_rep1
GSM4698216 Patient-Control_scRNAseq_rep2
This SubSeries is part of SuperSeries:
GSE133417 A Congenital Anemia Dissociates the Pleiotropic Functions of Master Transcription Factor GATA1
Relations
BioProject PRJNA649168
SRA SRP273926

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
GSE155254_RAW.tar 134.5 Mb (http)(custom) TAR (of MTX, TSV)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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