PXD032975-1

PXD032975 is an original dataset announced via ProteomeXchange.

Title	dCas9 targeted chromatin and histone enrichment for mass spectrometry (Catchet-MS) identifies IKZF1 as a novel target for HIV-1 latency reversal
Description	HIV-1 infected patients virally suppressed by antiviral treatment harbor a persistent reservoir of replication competent latent HIV-1 infected cells, which constitute the main roadblock to a cure. A main strategy for HIV cure aims to stimulate viral gene expression in latently infected cells so that they can be cleared. Crucial for the design of drugs referred to as “latency-reversing agents” (LRAs) is the identification of molecular targets for latency reversal. The regulatory factors physically associated with and repressing the latent HIV-1 promoter or 5’LTR would provide ideal putative molecular targets for latency reversal. However, due to technical limitations, the comprehensive and unbiased identification of host proteins associated with the latent or active integrated HIV LTR in infected cells not been possible. Here we use dCas9 targeted chromatin and histone enrichment strategy coupled to mass spectrometry (Catchet-MS), to purify the locus-associated dCas9 bait, guided downstream of the HIV-1 transcriptional start site (TSS) in latent and activated HIV-1 infected T cells to identify the 5’LTR bound latent and active regulatory complexes. Catchet-MS identified both previously described as well as novel host factors distinctly associated with the latent versus transcriptionally active HIV-1 5’LTR. Within the identified factors we find the transcription factor IKZF1 to be a novel repressor of the HIV-1 promoter required for maintenance of latency, and thus a molecular target for latency reversal. Finally, we identify the FDA approved drug, Iberdomide, which targets IKZF1 for degradation to be a novel LRA, which reversed latency in latent ex vivo HIV-1 infected primary CD4+ T cells and in cells isolated from HIV-1 infected, aviremic participants.
HostingRepository	PRIDE
AnnounceDate	2022-05-31
AnnouncementXML	Submission_2022-05-31_01:46:33.692.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jeroen Demmers
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-04-03 08:09:52	ID requested
⏵ 1	2022-05-31 01:46:34	announced

Dataset with its publication pending

submitter keyword: IKZF1, HIV-1 latency reversal, Catchet-MS

Jeroen Demmers
contact affiliation	Proteomics Center, Erasmus MC, Rotterdam
contact email	j.demmers@erasmusmc.nl
lab head
Jeroen Demmers
contact affiliation	Proteomics Center, Erasmus University Medical Center, Rotterdam, The Netherlands
contact email	j.demmers@erasmusmc.nl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD032975
     1. Label: PRIDE project
     2. Name: dCas9 targeted chromatin and histone enrichment for mass spectrometry (Catchet-MS) identifies IKZF1 as a novel target for HIV-1 latency reversal