PXD030581-2

PXD030581 is an original dataset announced via ProteomeXchange.

Title	HMG20B stabilizes interaction of LSD1 with GFI1 on chromatin to confer 1 transcription repression and leukemia cell differentiation block
Description	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.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:40:04.166.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Andrew Williamson
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2021-12-21 12:36:30	ID requested
1	2023-03-11 01:50:15	announced
⏵ 2	2023-11-14 08:40:06	announced	2023-11-14: Updated project metadata.

Maiques-Diaz A, Nicosia L, Basma NJ, Romero-Camarero I, Camera F, Spencer GJ, Amaral FMR, Simeoni F, Wingelhofer B, Williamson AJK, Pierce A, Whetton AD, Somervaille TCP, HMG20B stabilizes association of LSD1 with GFI1 on chromatin to confer transcription repression and leukemia cell differentiation block. Oncogene, 41(44):4841-4854(2022) [pubmed]

submitter keyword: Human LTQ Orbitrap Velos

Tim Somervaille
contact affiliation	Leukaemia Biology Laboratory, Cancer Research UK Manchester Institute, The University of Manchester, Manchester Cancer Research Centre Building, 555 Wilmslow Road, Manchester, M20 4GJ, United Kingdom
contact email	tim.somervaille@cruk.manchester.ac.uk
lab head
Andrew Williamson
contact affiliation	Thermo Fisher Scientific
contact email	andrew.williamson@thermofisher.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/03/PXD030581

PRIDE project URI

• PRIDE
  1. PXD030581
     1. Label: PRIDE project
     2. Name: HMG20B stabilizes interaction of LSD1 with GFI1 on chromatin to confer 1 transcription repression and leukemia cell differentiation block