NCBI Logo
GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
          Go
Series GSE192974 Query DataSets for GSE192974
Status Public on Oct 06, 2022
Title HMG20B stabilizes interaction of LSD1 with GFI1 on chromatin to confer transcription repression and leukemia cell differentiation block [RNA-seq]
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Pharmacologic inhibition of LSD1 induces molecular and morphologic differentiation of blast cells in acute myeloid leukaemia (AML) patients harboring MLL gene translocations. In addition to its demethylase activity, LSD1 has a critical scaffolding function at genomic sites occupied by the SNAG domain transcription repressor GFI1. Importantly, inhibitors block both enzymatic and scaffolding activities, in the latter case by disrupting the protein:protein interaction of GFI1 with LSD1. To explore the wider consequences of LSD1 inhibition on the LSD1 protein complex we made use of mass spectrometry approaches. We discovered that the interaction of the HMG-box protein HMG20B with LSD1 was also disrupted by LSD1 inhibition. Downstream investigations revealed that HMG20B is colocated on chromatin genome-wide with GFI1 and LSD1; the strongest HMG20B binding colocates with the strongest GFI1 and LSD1 binding. Functional assays demonstrated that HMG20B depletion induces leukaemia cell differentiation and further revealed that HMG20B is required for the transcription repressor activity of GFI1 through stabilizing the interaction on chromatin of LSD1 with GFI1. Interaction of HMG20B with LSD1 is through its coiled-coil domain. Thus, HMG20B is a critical component of the GFI1:LSD1 transcription repressor complex which contributes to leukaemia cell differentiation block.
 
Overall design Human THP1 AML cells were infected with a lentivirus targeting HMG20B for KD or a non-targeting control (NTC) and selected using puromycin. Cells were subjected to RNA-sequencing four days upon KD. Three replicated were analysed.
 
Contributor(s) Somervaille TC
Citation(s) 36171271
Submission date Jan 03, 2022
Last update date Nov 02, 2022
Contact name Tim C Somervaille
E-mail(s) tim.somervaille@cruk.manchester.ac.uk
Organization name Cancer Research UK
Department Manchester Institute
Lab Leukaemia Biology
Street address Wilmslow Rd
City Manchester
ZIP/Postal code M20 4BX
Country United Kingdom
 
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (6)
GSM5770042 TS89_01_NTC_1
GSM5770043 TS89_02_NTC_2
GSM5770044 TS89_03_NTC_3
This SubSeries is part of SuperSeries:
GSE192975 HMG20B stabilizes interaction of LSD1 with GFI1 on chromatin to confer transcription repression and leukemia cell differentiation block
Relations
BioProject PRJNA793915

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
GSE192974_RAW.tar 518.6 Mb (http)(custom) TAR (of BW)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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