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Series GSE153637 Query DataSets for GSE153637
Status Public on Mar 18, 2021
Title Transcriptional control of HP1a by the RNA binding proteins RBMX/L1 maintain chromatin state in myeloid leukemia
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary RNA binding proteins (RBPs) are key arbiters of post-transcriptional regulation that have been found to be dysregulated in hematological malignancies. Here, we identify the RBP RBMX and its retrogene RBMXL1 to be required for murine and human myeloid leukemogenesis. RBMX/L1 are overexpressed in acute myeloid leukemia (AML) primary patients compared to healthy individuals, and RBMX/L1 loss delayed leukemia development. Complex chromosomal karyotyping analysis and assay for transposase-accessible chromatin sequencing demonstrated that RBMX/L1 loss led to significant changes in chromatin accessibility and compaction. We found that RBMX/L1 directly binds to mRNAs and affects transcription of multiple loci, including the heterochromatin protein 1 alpha (HP1a) mRNA. Using single molecule resolution RNA fluorescence in situ hybridization, we uncovered that RBMX/L1 controls the nascent transcription of the HP1a locus. Forced HP1a expression rescued the RBMX/L1 depletion effects on cell growth and apoptosis. Overall, we determine that RBMX/L1 control leukemia cell survival by regulating chromatin state through its downstream target HP1a. These findings illuminate a novel mechanism for RBPs directly promoting transcription and suggest RBMX/L1 as well as HP1a as potential novel therapeutic targets in myeloid malignancies.
Overall design 21 human cell line samples,with RBMX/L1 KD and controls
Contributor(s) Prieto C, Nguyen D, Kharas M, Liu Z, Perez A
Citation(s) 34458856
Submission date Jul 01, 2020
Last update date Nov 03, 2021
Contact name Zhaoqi Liu
Phone 6466593600
Organization name Columbia university
Department Systems Biology
Lab The Rabadan Lab
Street address ICRC Building 8th Floor, Office 803B 1130 St. Nicholas Ave
City NewYork
State/province New York
ZIP/Postal code 10032
Country USA
Platforms (1)
GPL20301 Illumina HiSeq 4000 (Homo sapiens)
Samples (21)
GSM4648516 RNAseq_Control_1
GSM4648517 RNAseq_Control_2
GSM4648518 RNAseq_Control_3
BioProject PRJNA643547
SRA SRP269589

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Supplementary file Size Download File type/resource
GSE153637_RAW.tar 32.0 Mb (http)(custom) TAR (of TXT)
GSE153637_RBMX_kd_MOLM13_RNA-seq_48hr_processed_data.xlsx 5.7 Mb (ftp)(http) XLSX
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Raw data are available in SRA
Processed data are available on Series record
Processed data provided as supplementary file

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