Ask about this productRelated genes to: PDS5A Blocking Peptide
- Gene:
- PDS5A NIH gene
- Name:
- PDS5 cohesin associated factor A
- Previous symbol:
- -
- Synonyms:
- KIAA0648, PIG54, SCC-112
- Chromosome:
- 4p14
- Locus Type:
- gene with protein product
- Date approved:
- 2007-06-20
- Date modifiied:
- 2014-11-19
Related products to: PDS5A Blocking Peptide
Related articles to: PDS5A Blocking Peptide
- Cohesin orchestrates gene expression via three-dimensional chromosome folding. Genes encoding cohesin and cohesin loaders have been associated with Mendelian disorders, whereas genes encoding cohesin release factors, including WAPL and its binding partners PDS5A and PDS5B, have not. We explored the relevance of cohesin release factors in Mendelian disease by phenotyping individuals with heterozygous predicted damaging variants in WAPL (n = 27), PDS5A (n = 8), and PDS5B (n = 8), by modeling WAPL deficiency in human cells and mice, and by aggregating disease association statistics from consortia studies. We identified a WAPL-related disorder featuring developmental delay, intellectual disability, and risk of other developmental anomalies. Similarities between individuals with damaging WAPL variants and those with large, recurrent 10q22.3q23.2 (10q) deletions encompassing WAPL nominate WAPL as a driver gene within this genomic disorder region. While individuals with PDS5A or PDS5B variants exhibited features of developmental disorders, neither cohort-based statistics nor subject phenotyping associated these genes with specific phenotypes. We used CRISPR to generate truncating variants in WAPL and 10q deletion or duplication in human induced pluripotent stem cells (iPSCs) and induced neurons. Transcriptomics identified significant overlap between WAPL haploinsufficiency and 10q deletion differentially expressed genes. Mice with 50% Wapl expression exhibited mild deficits of growth and learning/memory, whereas those with 25% residual Wapl displayed birth defects and postnatal lethality, revealing a dosage liability threshold below the level of heterozygosity. In summary, we delineated a genetic condition caused by cohesin release factor deficiency, nominated WAPL as a driver gene within a genomic disorder region, and further illuminated dosage sensitivity of human cohesin. - Source: PubMed
Publication date: 2026/07/10
Boone Philip MErdin SerkanMohamed AbucarHaghshenas SadeghehFaour Kamli N WKao EmelineFu JackAuwerx ChiaraHarripaul RicardoJana BimalSpringer DanielleHallstrom Greyde Esch Celine E FDenhoff EricaHolmes LaurenMohajeri KianaLemanski JohnKerkhof JenniferMcConkey HaleyRzasa JessicaMcCune Madison JLevy Michael AGrafstein JuliaLarson MatthewWright ZsabreBeauchamp Roberta LLucente DianeJamra Rami AbouAgrawal NeenaAgrawal Pankaj BAndersen Erica FArgilli EmanuelaAraiza ReneeBallal SoniaBaxter Megan FBergant GaberBertsche AstridBhavsar RiyaBortola Debora RBothe ViktoriaBrasch-Andersen CharlotteBraun DominiqueBruel Ange-LineBuchanan CatherineBurt Nicholas DCarvalho Laura M LChiriatti LuigiCogne BenjaminCollins RyanCrunk AmyCurrall BenjaminDelahaye-Duriez AndreeDelanne JulianDenommé-Pichon Anne-SophieDevriendt KoenraadDomingo AloysiusDuncan LauraFaivre LaurenceFamularo LauraFulton AnneGenetti Casie AHarel TamarHavlovicova MarketaHiggs JennyHoulier MarineIascone MariaImmken LaDonnaIsidor BertrandKaiser Frank JKarbone KayceeKenna MargaretKhan AmjadKimmig Lara KristinaKleefstra TjitskeKraus Eva-MariaKrepischi Ana C VKrey IlonaLadda Roger LLanoue LouiseLe Caignec CedricLewis Zoe KLima GloriaLynch Sally AnnMacek MilanMaier OlivierMaitz SilviaMale AlisonMalikova MarcelaMcKay VictoriaMoldovan OanaMonteil DanielleOliveira Mariana MoysésMunasinghe JeevaNakamori SachikoNeuser SonjaNizon MathildeNuttle XanderO'Keefe KathrynOrec LauraParenti IlariaPeterlin BorutPfundt RolphPouncey JillRadio Francesca ClementinaRobert LeemaRodan LanceRosenberg-Fogler HallelRosenfeld Jill ASafraou HanaSalani MonicaSchliesske SophiaSeaby Eleanor GSell Susan LShearer A EliotSherr ElliottShillington AmelleSiebold DorotheaSinnema MargjeSmith LauraStegmann Alexander P AStevens Cathy AStevens Servi J CSurette EricTartaglia MarcoTaylor Jenny CThompson Michelle LTørring Pernille MTran Mau Them FredericTsoulaki OlgaUmair MuhammadVanhoutte ElsVincent MarieVitobello Antoniovon Wintzingerode LydiaWatt AmyWayhelova MarketaWentzensen Ingrid MWilson WilliamWojcik Monica HYuan BoZampino GiuseppeSrivastava SiddharthWestphal Dominik SRiedhammer Korbinian MJoyce EricYadav RachitaGusella James FTai Derek J CSadikovic BekimPfeifer Karl ETalkowski Michael E - Feed efficiency (FE) and growth traits are key determinants of profitability in the chicken industry. Using genome-wide association studies (GWAS) in 432 Wenchang chickens, we identified 28 significant and 1,063 suggestive genes associated with 6 FE and growth traits. We conducted colocalization analyses between GWAS loci and cis-eQTLs and detected 4 GWAS loci with 4 unique eGenes including LAP3, PDS5A, KLHL5 and KLB. We also examined the cis-eQTL analysis results of ChickenGTEx and integrated them with the results of our GWAS, which detected two SNPs (4_75971034, 4_75971177) regulating LAP3. Moreover, two significant InDels (4_75971045, 4_75971140) are identified in the LAP3 gene using GWAS, three genotypes significantly affecting the expression levels of this gene in transcriptomic analyses of 114 liver tissues, and highly linked to two SNPs, so these InDels may also affect LAP3. Our findings reveal key genetic variants and genes, contributing to a deeper elucidation of the molecular mechanisms that drive FE and growth traits in chickens. - Source: PubMed
Publication date: 2026/05/25
Zhang YapengZhang YinLuo NaCai KeqiLiang XiaochenLan YiLiu RanranZhao Guiping - Quantitative interpretation of ChIP-seq data is instrumental to derive insight into chromatin and transcription factor biology. Here we developed ChIP-FRiP, an end-to-end pipeline enabling systematic comparison of pairwise protein positioning, and applied it to the study of cohesin. In mammalian interphase, loop extruding cohesin complexes are positioned by CTCF barriers to generate locus-specific 3D genome folding patterns. Many aspects of our understanding of cohesin loop extrusion come from interpreting the amount of cohesin ChIP-seq signal at CTCF barriers, which has been reported to change variably after perturbing cohesin co-factors, such as NIPBL, PDS5A/B, and WAPL. Using ChIP-FRiP to homogeneously process 140 cohesin ChIP-seq datasets from 13 publicly available studies, we observed substantial variation attributable to technical effects, obscuring biological interpretability. To better understand how technical considerations, such as antibody specificity, influence apparent cohesin binding patterns, we integrated technical aspects of ChIP-seq into biophysical simulations of loop extrusion. Leveraging a simple biochemical model for background ChIP-seq signal, we derived a strategy to estimate and correct for the background using paired spike-in ChIP-seq data from wild-type and depletion conditions. Our results establish a framework for reliable comparative analysis, demonstrating that accurate background correction is requisite for interpreting the roles of cohesin cofactors in cohesin positioning. - Source: PubMed
Publication date: 2026/02/27
Xiao YaoAnderson Erika CRahmaninejad HadiNora ElphègeFudenberg Geoffrey - Cohesin-NIPBL complexes extrude genomic DNA into loops that are constrained by CTCF boundaries. This process has important regulatory functions and weakens the separation between euchromatic and heterochromatic compartments. Cohesin can also bind PDS5 proteins, which do not support loop extrusion but are required for the formation of CTCF boundaries. How PDS5 proteins perform this function is unknown. Here we show, by in vitro single-molecule imaging, that human PDS5 proteins stop loop extrusion by facilitating the dissociation of NIPBL from cohesin. Hi-C experiments suggest that this function is required for the establishment of CTCF boundaries in cells. In silico modeling indicates that PDS5 proteins enable the separation between compartments by limiting cohesin's velocity and chromatin residence time. The degree of this compartmentalization depends on the frequency with which chromatin is extruded relative to the time it takes for compartments to form. These results identify PDS5 proteins as key regulators of genome organization. - Source: PubMed
Publication date: 2026/04/23
Wutz GordanaDavidson Iain FBanigan Edward JStocsits Roman RKawasumi RyotaroTang WenNagasaka KotaCostantino LorenzoJansen RalfHirota KoujiBranzei DanaMirny Leonid APeters Jan-Michael - Three-dimensional (3D) genome organization is dynamically restructured during early vertebrate development, yet how chromatin domains are established remains poorly understood. In particular, the contribution of individual cohesin regulators to this process during embryogenesis is unclear. PDS5 proteins are key modulators of cohesin dynamics, but their depletion has been reported to cause context-dependent and sometimes contrasting architectural effects in cultured cells. Here, we investigated the roles of the cohesin regulators Pds5a and Pds5b during early development using the medaka embryo. Developmental transcriptome analysis revealed distinct but overlapping expression dynamics of pds5a and pds5b around the transition from zygotic genome activation to gastrulation. Morpholino-mediated depletion of either paralog resulted in only mild morphological phenotypes, whereas simultaneous depletion caused more severe developmental defects. In situ Hi-C analysis showed that single depletion of pds5a or pds5b induced only modest changes in 3D genome organization. In contrast, double depletion led to pronounced architectural alterations, including increased long-range chromatin contacts and de novo formation of extended chromatin loops. Transcriptome analysis revealed largely shared, with some condition-specific, gene expression changes in both single- and double-knockdown embryos, indicating that transcriptional effects can occur even in the absence of major architectural disruption. Together, our findings demonstrate that Pds5a and Pds5b act cooperatively to constrain cohesin-mediated long-range interactions during embryogenesis and highlight the importance of analyzing cohesin regulator function within a developmental context to understand how 3D genome organization is established in vivo. - Source: PubMed
Ikeda ShinraTakeda HiroyukiNakamura Ryohei