Ask about this productRelated genes to: PPHLN1 Blocking Peptide
- Gene:
- PPHLN1 NIH gene
- Name:
- periphilin 1
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 12q12
- Locus Type:
- gene with protein product
- Date approved:
- 2002-11-04
- Date modifiied:
- 2006-10-24
Related products to: PPHLN1 Blocking Peptide
Related articles to: PPHLN1 Blocking Peptide
- The human silencing hub (HUSH) maintains the genome integrity by silencing invasive genetic elements. However, despite essential roles of the HUSH complex during early embryonic development, the function of the complex in the maintenance of pluripotency is mostly unknown. Here, using CRISPR-based genome editing, we demonstrate that in mouse embryonic stem cells (mESCs), deficiency of HUSH core members MPP8 or TASOR, but not PPHLN1, triggers alteration of colony morphology, and mild defect in exit from pluripotency. Importantly, Mpp8/Tasor double mutants are locked in pluripotent state even upon differentiation stimuli. We further demonstrate that these phenotypes are accompanied by decreased expression of adhesion-related genes. Strikingly, the abnormalities observed in Mpp8/Tasor-null mESCs were largely rescued by ectopic coexpression of cell-adhesion associated genes keratins 18 and 19. Thus, our study provides new insights into the mechanisms by which the HUSH complex coordinates the exit from pluripotency through regulation of the cell adhesion machinery. - Source: PubMed
Publication date: 2025/11/25
Wang BowenQi MinSun YanqiLiao HuaqiXu YuzhuoDong LixiaXu LijunXia YinJiang XiaochunLing ShizhangQin Jinzhong - Human endogenous retroviruses (hERVs) are noninfectious molecular remnants of ancient exogenous retroviruses that now make up 8% of the human genome. The ubiquitously expressed human locus was recently annotated as encoding a 109-amino acid endogenous retroviral Rec microprotein. However, because this locus was thought to be noncoding until recently, it is currently unknown whether the ERVK3-1 microprotein has a function in human cells. We demonstrate that the ERVK3-1 microprotein interacts with PPHLN1, a component of the HUSH complex. The HUSH complex promotes transcriptional repression of intron-less genes, which include parasitic genomic elements such as retrotransposons and endogenous retroviruses. We show that the ERVK3-1 microprotein is essential for transcriptional repression of previously identified HUSH target genes. We thus suggest that the ERVK3-1 Rec microprotein contributes to sensing or regulation of target gene expression by the HUSH complex. - Source: PubMed
Publication date: 2025/07/23
Jayatissa AyodyaJaunbocus NadiyaErkalo BetelJiang KevinZheng Shu-JianSu HaomiaoYan LichongChoi Jin-YoungVaughan JoanBacchiocchi AntonellaNa ZhenkunCao XiongwenHalaban RuthSaghatelian AlanCraft JosephChen Y GraceSlavoff Sarah A - Genome-wide association studies (GWASs) have identified tens of thousands of disease associated variants and provided critical insights into developing effective treatments. However, limited sample sizes have hindered the discovery of variants for uncommon and rare diseases. Here, we introduce KGWAS, a novel geometric deep learning method that leverages a massive functional knowledge graph across variants and genes to improve detection power in small-cohort GWASs significantly. KGWAS assesses the strength of a variant's association to disease based on the aggregate GWAS evidence across molecular elements interacting with the variant within the knowledge graph. Comprehensive simulations and replication experiments showed that, for small sample sizes ( =1-10K), KGWAS identified up to 100% more statistically significant associations than state-of-the-art GWAS methods and achieved the same statistical power with up to 2.67× fewer samples. We applied KGWAS to 554 uncommon UK Biobank diseases ( <5K) and identified 183 more associations (46.9% improvement) than the original GWAS, where the gain further increases to 79.8% for 141 rare diseases (N <300). The KGWAS-only discoveries are supported by abundant functional evidence, such as rs2155219 (on 11q13) associated with ulcerative colitis potentially via regulating expression in CD4+ regulatory T cells, and rs7312765 (on 12q12) associated with the rare disease myasthenia gravis potentially via regulating expression in neuron-related cell types. Furthermore, KGWAS consistently improves downstream analyses such as identifying disease-specific network links for interpreting GWAS variants, identifying disease-associated genes, and identifying disease-relevant cell populations. Overall, KGWAS is a flexible and powerful AI model that integrates growing functional genomics data to discover novel variants, genes, cells, and networks, especially valuable for small cohort diseases. - Source: PubMed
Publication date: 2024/12/05
Huang KexinZeng TonyKoc SonerPettet AlexandraZhou JingtianJain MikaSun DongboRuiz CamiloRen HongyuHowe LaurenceRichardson Tom GCortes AdrianAiello KatieBranson KimPfenning AndreasEngreitz Jesse MZhang Martin JinyeLeskovec Jure - An obligate step in the life cycle of HIV-1 and other retroviruses is the establishment of the provirus in target cell chromosomes. Transcriptional regulation of proviruses is complex, and understanding the mechanisms underlying this regulation has ramifications for fundamental biology, human health, and gene therapy implementation. The three core components of the Human Silencing Hub (HUSH) complex, TASOR, MPHOSPH8 (MPP8), and PPHLN1 (Periphilin 1), were identified in forward genetic screens for host genes that repress provirus expression. Subsequent loss-of-function screens revealed accessory proteins that collaborate with the HUSH complex to silence proviruses in particular contexts. To identify proteins associated with a HUSH complex-repressed provirus in human cells, we developed a technique, Provirus Proximal Proteomics, based on proximity labeling with C-BERST (dCas9-APEX2 biotinylation at genomic elements by restricted spatial tagging). Our screen exploited a lentiviral reporter that is silenced by the HUSH complex in a manner that is independent of the integration site in chromatin. Our data reveal that proviruses silenced by the HUSH complex are associated with DNA repair, mRNA processing, and transcriptional silencing proteins, including L3MBTL2, a member of the non-canonical polycomb repressive complex 1.6 (PRC1.6). A forward genetic screen confirmed that PRC1.6 components L3MBTL2 and MGA contribute to HUSH complex-mediated silencing. PRC1.6 was then shown to silence HUSH-sensitive proviruses in a promoter-specific manner. Genome wide profiling showed striking colocalization of the PRC1.6 and HUSH complexes on chromatin, primarily at sites of active promoters. Finally, PRC1.6 binding at a subset of genes that are silenced by the HUSH complex was dependent on the core HUSH complex component MPP8. These studies offer new tools with great potential for studying the transcriptional regulation of proviruses and reveal crosstalk between the HUSH complex and PRC1.6. - Source: PubMed
Publication date: 2024/07/13
Rodríguez Tomás CYurkovetskiy LeonidNagalekshmi KarthikaLam Chin Hung OscarJazbec EvaMaitland Stacy AWolfe Scot ASontheimer Erik JLuban Jeremy - OTX2 is a transcription factor and known driver in medulloblastoma (MB), where it is amplified in a subset of tumours and overexpressed in most cases of group 3 and group 4 MB. Here we demonstrate a noncanonical role for OTX2 in group 3 MB alternative splicing. OTX2 associates with the large assembly of splicing regulators complex through protein-protein interactions and regulates a stem cell splicing program. OTX2 can directly or indirectly bind RNA and this may be partially independent of its DNA regulatory functions. OTX2 controls a pro-tumorigenic splicing program that is mirrored in human cerebellar rhombic lip origins. Among the OTX2-regulated differentially spliced genes, PPHLN1 is expressed in the most primitive rhombic lip stem cells, and targeting PPHLN1 splicing reduces tumour growth and enhances survival in vivo. These findings identify OTX2-mediated alternative splicing as a major determinant of cell fate decisions that drive group 3 MB progression. - Source: PubMed
Publication date: 2024/07/18
Saulnier OlivierZagozewski JamieLiang LisaHendrikse Liam DLayug PaulGordon VictorAldinger Kimberly AHaldipur ParthivBorlase StephanieCoudière-Morrison LudivineCai TingMartell EmmaGonzales Naomi MPalidwor GarethPorter Christopher JRichard StéphaneSharif TanveerMillen Kathleen JDoble Brad WTaylor Michael DWerbowetski-Ogilvie Tamra E