VPS72

Last update 08 May 2025

Basic Info

Synonyms

Protein YL-1, Swc2, TCFL1

+ [6]

Introduction

Deposition-and-exchange histone chaperone specific for H2AZ1, specifically chaperones H2AZ1 and deposits it into nucleosomes. As component of the SRCAP complex, mediates the ATP-dependent exchange of histone H2AZ1/H2B dimers for nucleosomal H2A/H2B, leading to transcriptional regulation of selected genes by chromatin remodeling.

100 Clinical Results associated with VPS72

100 Translational Medicine associated with VPS72

0 Patents (Medical) associated with VPS72

Literatures (Medical) associated with VPS72

01 Jan 2025·Cellular and Molecular Gastroenterology and Hepatology

In Vivo CRISPR Activation Screening Reveals Chromosome 1q Genes VPS72, GBA1, and MRPL9 Drive Hepatocellular Carcinoma

Article

Author: Cai, Chunmiao ; Lee, Markcus ; He, Shirui ; Chrystostome, Marie-Lise ; Vázquez Salgado, Alexandra M ; Kieckhaefer, Julia E ; Wangensteen, Kirk J ; Yin, Dingzi ; Gefre, Adrienne F

BACKGROUND & AIMSHepatocellular carcinoma (HCC) frequently undergoes regional chromosomal amplification, resulting in elevated gene expression levels. We aimed to elucidate the role of these poorly understood genetic changes by using CRISPR activation (CRISPRa) screening in mouse livers to identify which genes within these amplified loci are cancer driver genes.METHODSWe used data from The Cancer Genome Atlas to identify that frequently copy number-amplified and up-regulated genes all reside on human chromosomes 1q and 8q. We generated CRISPRa screening transposons that contain oncogenic Myc to drive tumor formation. We conducted CRISPRa screens in vivo in the liver to identify tumor driver genes. We extensively validated the findings in separate mice and performed RNA sequencing analysis to explore mechanisms driving tumorigenesis.RESULTSWe targeted genes that frequently undergo amplification in human HCC using an in vivo CRISPRa screening system in mice, which induced extensive liver tumorigenesis. Human chromosome 1q genes Zbtb7b, Vps72, Gba1, and Mrpl9 emerged as drivers of liver tumorigenesis. In human HCC there is a trend in correlation between levels of MRPL9, VPS72, or GBA1 and poor survival. In validation assays, activation of Vps72, Gba1, or Mrpl9 resulted in extensive liver tumorigenesis and decreased survival in mice. RNA sequencing revealed different mechanisms driving HCC, with Mrpl9 activation altering genes functionally related to mitochondrial function, Vps72 levels altering phospholipid metabolism, and Gba1 activation enhancing endosomal-lysosomal activity, all leading to promotion of cellular proliferation. Analysis of human tumor tissues with high levels of MRPL9, VPS72, or GBA1 revealed congruent results, indicating conserved mechanisms driving HCC.CONCLUSIONSThis study reveals chromosome 1q genes Vps72, Gba1, and Mrpl9 as drivers of HCC. Future efforts to prevent or treat HCC can focus on these new driver genes.

23 Dec 2024·The Plant Cell

Jasmonate induces translation of the Arabidopsis transfer RNA-binding protein YUELAO1, which activates MYC2 in jasmonate signaling

Article

Author: Hu, Yanru ; Zhu, Sirui ; Wang, Jiahui ; Li, Yuanyuan

AbstractJasmonate is ubiquitous in the plant kingdom and regulates multiple physiological processes. Although jasmonate signaling has been thoroughly investigated in Arabidopsis thaliana, most studies have focused on the transcriptional mechanisms underlying various jasmonate responses. It remains unclear whether (and how) translation-related pathways help improve transcription efficiency to modulate jasmonate signaling, which may enable plants to respond to stressful conditions effectively. Here, we demonstrate that jasmonate induces translation of the transfer RNA (tRNA)-binding protein YUELAO 1 (YL1) via a specific region in its 3′ untranslated region (3′ UTR). YL1 and its homolog YL2 redundantly stimulate jasmonate responses such as anthocyanin accumulation and root growth inhibition, with the YL1 3′ UTR being critical for YL1-promoted jasmonate responses. Once translated, YL1 acts as an activator of the MYC2 transcription factor through direct interaction, and disrupting YL1 3′ UTR impairs the YL1-mediated transcriptional activation of MYC2. YL1 enhances jasmonate responses mainly in a MYC2-dependent manner. Together, these findings reveal a translational mechanism involved in jasmonate signaling and advance our understanding of the transcriptional regulation of jasmonate signaling. The YL1 3′ UTR acts as a crucial signal transducer that integrates translational and transcriptional regulation, allowing plants to respond to jasmonate in a timely fashion.

05 Dec 2024·Nature

Nucleosome flipping drives kinetic proofreading and processivity by SWR1

Article

Author: Skehan, Michael T. ; Wigley, Dale B. ; Knight, Carol L. ; Rueda, David S ; Wigley, Dale B ; Skehan, Michael T ; Rueda, David S. ; Jalal, Adam S. B. ; McCormack, Elizabeth A. ; Knight, Carol L ; McCormack, Elizabeth A ; Girvan, Paul ; Jalal, Adam S B

AbstractThe yeast SWR1 complex catalyses the exchange of histone H2A–H2B dimers in nucleosomes, with Htz1–H2B dimers1–3. Here we used single-molecule analysis to demonstrate two-step double exchange of the two H2A–H2B dimers in a canonical yeast nucleosome with Htz1–H2B dimers, and showed that double exchange can be processive without release of the nucleosome from the SWR1 complex. Further analysis showed that bound nucleosomes flip between two states, with each presenting a different face, and hence histone dimer, to SWR1. The bound dwell time is longer when an H2A–H2B dimer is presented for exchange than when presented with an Htz1–H2B dimer. A hexasome intermediate in the reaction is bound to the SWR1 complex in a single orientation with the ‘empty’ site presented for dimer insertion. Cryo-electron microscopy analysis revealed different populations of complexes showing nucleosomes caught ‘flipping’ between different conformations without release, each placing a different dimer into position for exchange, with the Swc2 subunit having a key role in this process. Together, the data reveal a processive mechanism for double dimer exchange that explains how SWR1 can ‘proofread’ the dimer identities within nucleosomes.

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VPS72

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