Ask about this productRelated genes to: DNTTIP1 antibody
- Gene:
- DNTTIP1 NIH gene
- Name:
- deoxynucleotidyltransferase terminal interacting protein 1
- Previous symbol:
- C20orf167
- Synonyms:
- dJ447F3.4, Tdif1
- Chromosome:
- 20q13.12
- Locus Type:
- gene with protein product
- Date approved:
- 2001-07-17
- Date modifiied:
- 2016-07-20
Related products to: DNTTIP1 antibody
Related articles to: DNTTIP1 antibody
- Acute leukaemia is a highly aggressive malignancy with significant unmet therapeutic needs, partly due to epigenetic dysregulation. Here, we uncover deoxynucleotidyl transferase terminal-interacting protein 1 (DNTTIP1) within the mitotic deacetylase complex (MiDAC) as a previously unrecognised epigenetic regulator crucial for leukaemic cell survival and elucidate its mechanistic and translational significance. - Source: PubMed
Xiu RuolinMa YuzhuGao YueyingChen YaoLi XinyuWu YueSun MeilingLi QizhaoZhao YanhongXu ShuqianFan ShengjinLi YongshengFan Huitao - MIDEAS is a scaffold protein that, together with DNTTIP1, mediates assembly of the MiDAC histone deacetylase complex. Mice lacking MiDAC die before birth suggesting a key developmental function. Here, we report two unrelated individuals, with a multisystem disorder characterised by delayed speech development, joint contractures, dysmorphic features and dysmotility of the gut. Both individuals have the same de novo heterozygous missense variant in MIDEAS (p.Tyr654Ser). A cryoEM structure of the MiDAC complex reveals that this amino acid is located in a conserved auto-inhibitory loop that covers the active site of the deacetylase enzyme. We suggest that the variant results in loop displacement leading to elevated deacetylase activity. In support, we observe reciprocal gene expression changes in patient fibroblasts compared with a cell line following rapid MiDAC degradation. Our results establish MIDEAS as a dominant monogenic disease gene and that hyperactivity of the MiDAC complex results in a characteristic multisystem disorder. - Source: PubMed
Publication date: 2025/11/25
Fairall LouiseSirvydis KristupasTurnbull Robert EKnottnerus Suzan JgGonchar OksanaMuskett Frederick WJukes-Jones Rebekahvan Brussel Lonnekevan de Geer Ellenvan Gassen KoenBadenhorst PaulJohnson DianaTerhal Paulien Avan Hasselt Peter Mvan Jaarsveld Richard HSchwabe John Wr - This study aims to identify and validate a transcriptomic signature capable of predicting the response to tumour necrosis factor inhibitors (TNFi) therapy in patients with rheumatoid arthritis (RA) before treatment initiation. - Source: PubMed
Publication date: 2025/09/03
Santiago-Lamelas LuciaCastro-Santos PatriciadeAndrés-Galiana Enrique JFernández-Martínez Juan LuisEscudero-Contreras AlejandroPérez-Sanchez CarlosSánchez-Pareja IsmaelLópez-Pedrera CharyJelinsky Scott ANikitsina MaryiaGonzalez-Alvaro IsidoroSobrín Raquel Dos SantosMera AntonioDurán JosefinaDíaz-Peña Roberto - Histone deacetylase (HDAC) complexes regulate pathological gene programs during heart disease progression. The recently identified mitotic deacetylase complex (MiDAC), which includes DNTTIP1, ELMSAN1, and HDAC1/2, remains the least characterized among these complexes. ELMSAN1 has been implicated in left ventricular remodeling, and its global deletion in mice leads to heart malformation. To investigate its role in mouse heart, we generated cardiomyocyte-specific knockout (ELM cKO) using αMHC-driven Cre recombinase. We analyzed both male and female animals across three experimental groups: αMHC-Cre (Cre control), ELM fl/fl (floxed control), and ELM cKO. In male ELM cKO mice, ejection fraction (EF) was significantly reduced by 12 wk (45.64 ± 3.12%), compared with αMHC-Cre (55.91 ± 1.29%) and ELM fl/fl (59.16 ± 3.70%) controls. By 24 wk, EF declined further to 20.79 ± 4.52%, representing a reduction of 46.4% ( < 0.01) and 62.1% ( < 0.0001) compared with αMHC-Cre and ELM fl/fl mice, respectively. The heart failure phenotype in ELM cKO mice was supported by cardiomyocyte hypertrophy morphology, ventricular dilation, and shortened lifespan. Female ELM cKO mice exhibited similar defects with delayed onset. To investigate early molecular changes, we performed RNA sequencing on presymptomatic hearts from 8-wk-old mice. A total of 1,055 genes were differentially expressed in ELM ckO hearts, with 460 upregulated and 595 downregulated. Gene enrichment analysis revealed suppression of tricarboxylic acid cycle and key cardiac genes. These transcriptional changes were accompanied by decreased mitochondrial respiratory chain complex proteins, ultrastructural mitochondrial abnormalities, and impaired calcium handling. Our study demonstrates that Elmsan1 is pivotal for maintaining heart function and hemostasis with advanced age. Our study demonstrates that Elmsan1, a unique component of the mitotic deacetylase complex (MiDAC), is essential for maintaining cardiac function. Loss of in cardiomyocytes leads to age-related cardiac dysfunction and mitochondrial abnormalities in mice. Using a cardiomyocyte-specific knockout model, we show that Elmsan1 preserves adult heart function by regulating genes involved in calcium handling and energy metabolism, underscoring the specific role of MiDAC in maintaining heart hemostasis. - Source: PubMed
Publication date: 2025/06/30
Wang MeimeiLi HuiHan ChaoshanChen YunxiHe LihaoXie MinLal HindFast Vladimir GMoellering Douglas RZhang JianyiLu RuiYoung MartinZhou Yang - The human immunodeficiency virus (HIV) integrates into the host genome forming latent cellular reservoirs that are an obstacle for cure or remission strategies. Viral transcription is the first step in the control of latency and depends upon the hijacking of the host cell RNA polymerase II (Pol II) machinery by the 5' HIV LTR. Consequently, "block and lock" or "shock and kill" strategies for an HIV cure depend upon a full understanding of HIV transcriptional control. The HIV trans-activating protein, Tat, controls HIV latency as part of a positive feed-forward loop that strongly activates HIV transcription. The recognition of the TATA box and adjacent sequences of HIV essential for Tat trans-activation (TASHET) of the core promoter by host cell pre-initiation complexes of HIV (PICH) has been shown to be necessary for Tat trans-activation, yet the protein composition of PICH has remained obscure. Here, DNA-affinity chromatography was employed to identify the mitotic deacetylase complex (MiDAC) as selectively recognizing TASHET. Using biophysical techniques, we show that the MiDAC subunit DNTTIP1 binds directly to TASHET, in part via its CTGC DNA motifs. Using co-immunoprecipitation assays, we show that DNTTIP1 interacts with MiDAC subunits MIDEAS and HDAC1/2. The Tat-interacting protein, NAT10, is also present in HIV-bound MiDAC. Gene silencing revealed a functional role for DNTTIP1, MIDEAS, and NAT10 in HIV expression in cellulo. Furthermore, point mutations in TASHET that prevent DNTTIP1 binding block the reactivation of HIV by latency reversing agents (LRA) that act via the P-TEFb/7SK axis. Our data reveal a key role for MiDAC subunits DNTTIP1, MIDEAS, as well as NAT10, in Tat-activated HIV transcription and latency. DNTTIP1, MIDEAS and NAT10 emerge as cell cycle-regulated host cell transcription factors that can control activated HIV gene expression, and as new drug targets for HIV cure strategies. - Source: PubMed
Publication date: 2024/05/23
Wilhelm EmmanuellePoirier MikaëlDa Rocha MorganeBédard MikaëlMcDonald Patrick PLavigne PierreHunter Christie LBell Brendan