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Last update 08 May 2025

AHRR

Last update 08 May 2025

Basic Info

Synonyms

AHH, AHHR, AhR repressor

+ [6]

Introduction

Mediates dioxin toxicity and is involved in regulation of cell growth and differentiation. Represses the transcription activity of AHR by competing with this transcription factor for heterodimer formation with the ARNT and subsequently binding to the xenobiotic response element (XRE) sequence present in the promoter regulatory region of variety of genes. Represses CYP1A1 by binding the XRE sequence and recruiting ANKRA2, HDAC4 and/or HDAC5. Autoregulates its expression by associating with its own XRE site.

Drugs associated with AHRR

(±)-13e(Chinese Academy of Medical Sciences and Peking Union Medical College)

Target

AHRR

Mechanism

AHRR antagonists

Active Org.

Beijing Union Medical College Hospital, Chinese Academy of Medical Sciences

Originator Org.

Beijing Union Medical College Hospital, Chinese Academy of Medical Sciences

Active Indication

Neoplasms

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with AHRR

100 Translational Medicine associated with AHRR

0 Patents (Medical) associated with AHRR

1,239

Literatures (Medical) associated with AHRR

01 May 2025·Toxicology Letters

Cigarette smoking modulates m6A modification, affecting the induction of CYP1A1 mRNA by regulating human ARNT and AHRR in A549 cells

Article

Author: Nakajima, Miki ; Fukami, Tatsuki ; Nakano, Takumi ; Nakano, Masataka

N⁶-Methyladenosine (m⁶A) modification is a common epitranscriptomic mark of eukaryotic RNAs. This modification is installed by a methyltransferase like 3 (METTL3)-METTL14 complex and is eliminated by fat mass and obesity-associated protein (FTO) and AlkB homolog 5 (ALKBH5). Aberrant m⁶A modification is associated with the development and progression of cancer. Cigarette smoking is a major lifestyle habit and risk factor for lung cancer. This study aimed to clarify the effects of cigarette smoking on the expression of m⁶A modification-regulating enzymes and the significance of m⁶A modification in the biological responses to cigarette smoking. Treatment of cigarette smoke extract (CSE) significantly decreased METTL3 and METTL14 protein levels in human lung adenocarcinoma-derived A549 cells. The induction of CYP1A1 mRNA by 2,3,7,8-tetrachlorodibenzo-p-dioxin, a typical ligand of the aryl hydrocarbon receptor (AHR), was attenuated by the knockdown (KD) of METTL3 or ALKBH5, whereas it was enhanced by the KD of FTO. As the underlying mechanisms, significantly decreased expression of AHR nuclear translocator (ARNT) by the KD of METTL3 or ALKBH5, and significantly decreased expression of AHR repressor (AHRR) by the KD of FTO were demonstrated. Formaldehyde-assisted isolation of regulatory elements assay revealed that the KD of METTL3 or ALKBH5 resulted in the compaction of the chromatin structure of ARNT promoter, suggesting that METTL3 and ALKBH5 promote the transcription of ARNT through the rearrangement of chromatin structure. Collectively, we found that CSE treatment decreased METTL3 and METTL14 protein levels, and m⁶A modification have impact on the induction of CYP1A1 by modulating ARNT and AHRR expression.

01 Feb 2025·Journal of Psychiatric Research

Potential metabolic sequelae to the terrorist attack of October 7th, 2023

Review

Author: Maayan, Lawrence ; Kalanthroff, Eyal ; Neria, Yuval ; Cohen, Ezra

OBJECTIVE/HYPOTHESISEvaluate cardiometabolic risk as a potential sequel to a mass terrorist attack using October 7th, 2023 as a focus.METHODSNarrative review surveying PubMed, PsycNet, UN and Council on Foreign Relations websites on. 1. PTSD following terrorism, rocket attacks and conflict related sexual violence. 2. The relationship between cardiometabolic illness and PTSD. 3. Humoral, genetic and epigenetic mechanisms relating cardiometabolic risk, inflammation and PTSD. 4. Treatments for PTSD and associated cardiometabolic risk factors and their effectiveness.FINDINGSCardiometabolic sequelae occur after trauma. This is most pronounced when trauma, sexual or violence related, occurs during childhood. The risk of cardiometabolic sequelae increases with PTSD diagnosis in adults. Inflammation as well as genes related to inflammatory function (e.g. FKBP5, AHRR, NR3C1) impact vulnerability to PTSD, response to treatment and cardiometabolic outcomes. Treatments for PTSD appear somewhat more effective at lowering cardiometabolic risk in civilian, rather than military populations. There is little published research on directly treating cardiometabolic sequelae of PTSD.CONCLUSIONSIsraelis, particularly those with exposure to the terror events of October 7, 2023 should be screened for psychological and metabolic sequelae. This should occur in a primary care setting and be part of observational research to help understand relationships between trauma, metabolic outcomes and their treatment.

22 Jan 2025·Epigenomics

Impact of excess sugar on the whole genome DNA methylation pattern in human sperm

Article

Author: Ling, Charlotte ; Jönsson, Josefine ; Kugelberg, Unn ; Ruhrmann, Sabrina ; Lindström, Axel ; Öst, Anita ; Perfilyev, Alexander ; Bacos, Karl ; Rönn, Tina ; Skog, Signe ; Ofori, Jones K.

AIMS, PATIENTS & METHODSDietary factors may regulate the epigenome. We aimed to explore whether a diet intervention, including excess sugar, affects the methylome in human sperm, and to describe the sperm methylome. We used Whole Genome Bisulfite Sequencing (WGBS) to analyze DNA methylation in sperm taken at three time points from 15 males during a diet intervention; i) at baseline, ii) after one week on a standardized diet, and iii) after an additional week on a high-sugar diet providing 150% of their estimated total energy expenditure.RESULTSWe identified seven nominal diet-associated differentially methylated regions in sperm (p < 0.05). The diet was nominally associated with methylation of 143 sites linked to fertility (e.g. AHRR, GNAS, and HDAC4), 313 sites in imprinted genes (e.g. GLIS3, PEG10, PEG3, and SNURF), and 42 sites in top 1%-expressed genes (e.g. CHD2) (p < 0.05). In sperm, 3'UTRs and introns had the highest levels of methylation, while 5'UTRs and CpG islands had the lowest levels. Non-expressed genes in human sperm were hypomethylated in exons compared with transcribed genes.CONCLUSIONSIn human sperm, DNA methylation levels were linked to gene expression, and excess sugar had modest effects on methylation on imprinted and highly expressed genes, and genes affecting fertility.

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