PRDM8

Last update 08 May 2025

Basic Info

Synonyms

KMT8D, PFM5, PR domain zinc finger protein 8

+ [3]

Introduction

Probable histone methyltransferase, preferentially acting on 'Lys-9' of histone H3 (By similarity). Involved in the control of steroidogenesis through transcriptional repression of steroidogenesis marker genes such as CYP17A1 and LHCGR (By similarity). Forms with BHLHE22 a transcriptional repressor complex controlling genes involved in neural development and neuronal differentiation (By similarity). In the retina, it is required for rod bipolar and type 2 OFF-cone bipolar cell survival (By similarity).

100 Clinical Results associated with PRDM8

100 Translational Medicine associated with PRDM8

0 Patents (Medical) associated with PRDM8

Literatures (Medical) associated with PRDM8

01 Jan 2025·Molecular Cell

Long-range regulation of transcription scales with genomic distance in a gene-specific manner

Article

Author: Jensen, Christina L ; Bassik, Mike C ; Yao, David ; Boettiger, Alistair N ; Wysocka, Joanna ; Swigut, Tomek ; Chen, Liang-Fu ; Crocker, Olivia J ; Ferrell, James E

Although critical for tuning the timing and level of transcription, enhancer communication with distal promoters is not well understood. Here, we bypass the need for sequence-specific transcription factors (TFs) and recruit activators directly using a chimeric array of gRNA oligos to target dCas9 fused to the activator VP64-p65-Rta (CARGO-VPR). We show that this approach achieves effective activator recruitment to arbitrary genomic sites, even those inaccessible when targeted with a single guide. We utilize CARGO-VPR across the Prdm8-Fgf5 locus in mouse embryonic stem cells (mESCs), where neither gene is expressed. Although activator recruitment to any tested region results in the transcriptional induction of at least one gene, the expression level strongly depends on the genomic distance between the promoter and activator recruitment site. However, the expression-distance relationship for each gene scales distinctly in a manner not attributable to differences in 3D contact frequency, promoter DNA sequence, or the presence of repressive chromatin marks at the locus.

01 May 2024·Journal of Neurology

Genome-wide DNA methylation analysis related to ALS patient progression and survival

Article

Author: Shang, Huifang ; Yang, Tianmi ; Xiao, Yi ; Pang, Dejiang ; Wang, Shichan ; Li, Chunyu ; Lin, Junyu ; Cheng, Yangfan ; Huang, Jingxuan ; Jiang, Qirui ; Wei, Qianqian

BACKGROUNDEpigenetics contributes to the pathogenesis of amyotrophic lateral sclerosis (ALS). We aimed to characterize the DNA methylation profiles associated with clinical heterogeneity in disease progression and survival among patients.METHODSWe included a cohort of 41 patients with sporadic ALS, with a median follow-up of 86.9 months, and 27 rigorously matched healthy controls. Blood-based genome-wide DNA methylation analysis was conducted.RESULTSA total of 948 progression rate-associated differentially methylated positions, 298 progression rate-associated differentially methylated regions (R-DMRs), 590 survival time-associated DMPs, and 197 survival time-associated DMRs (S-DMRs) were identified, using complementary grouping strategies. Enrichment analysis of differentially methylated genes highlighted the involvement of synapses and axons in ALS progression and survival. Clinical analysis revealed a positive correlation between the average methylation levels of the R-DMR in PRDM8 and disease progression rate (r = 0.479, p = 0.002). Conversely, there was an inverse correlation between the average methylation levels of the R-DMR in ANKRD33 and disease progression rate (r = - 0.476, p = 0.002). In addition, patients with higher methylation levels within the S-DMR of ZNF696 experienced longer survival (p = 0.016), while those with elevated methylation levels in the S-DMR of RAI1 had shorter survival (p = 0.006).CONCLUSIONDNA methylation holds promise as a potential biomarker for tracking disease progression and predicting survival outcome and also offers targets for precision medicine.

17 Oct 2023·Human molecular genetics

Mutations in human DNA methyltransferase DNMT1 induce specific genome-wide epigenomic and transcriptomic changes in neurodevelopment.

Article

Author: Ma, Shining ; Davis, Kasey N ; Urban, Alexander E ; Plazzi, Giuseppe ; Zhang, Xianglong ; Hallmayer, Joachim ; Pizza, Fabio ; Wong, Wing Hung ; Dahl, Niklas ; Lin, Ling ; O'Hara, Ruth ; Qu, Ping-Ping ; Mignot, Emmanuel ; Plastini, Melanie

DNA methyltransferase type 1 (DNMT1) is a major enzyme involved in maintaining the methylation pattern after DNA replication. Mutations in DNMT1 have been associated with autosomal dominant cerebellar ataxia, deafness and narcolepsy (ADCA-DN). We used fibroblasts, induced pluripotent stem cells (iPSCs) and induced neurons (iNs) generated from patients with ADCA-DN and controls, to explore the epigenomic and transcriptomic effects of mutations in DNMT1. We show cell type-specific changes in gene expression and DNA methylation patterns. DNA methylation and gene expression changes were negatively correlated in iPSCs and iNs. In addition, we identified a group of genes associated with clinical phenotypes of ADCA-DN, including PDGFB and PRDM8 for cerebellar ataxia, psychosis and dementia and NR2F1 for deafness and optic atrophy. Furthermore, ZFP57, which is required to maintain gene imprinting through DNA methylation during early development, was hypomethylated in promoters and exhibited upregulated expression in patients with ADCA-DN in both iPSC and iNs. Our results provide insight into the functions of DNMT1 and the molecular changes associated with ADCA-DN, with potential implications for genes associated with related phenotypes.

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PRDM8

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