2/29/2024 0 Comments Otx logistics billings mt![]() 7 Each receptor subfamily has a preferred HRE motif it binds, although significant variation has been observed in the ability of NHRs to bind to particular HRE sequences ( Table 1). HREs are small sequences of DNA commonly located near the promoter region of a gene, yet they may also be found up to several hundred kilobases upstream of the promoter and even within the first intron of a gene. Nerve growth factor IB-like receptor (NR4A1) 6 A collection of HREs and coregulators and corepressors for each nuclear receptor is given in Table 1. 6 Receptors use several mechanisms such as interaction with the HREs, coregulators, interaction with the transcription factor complex, and histone modification to finely orchestrate an appropriate gene expression. Coregulators facilitate or truncate the receptors’ ability to bind to the transcriptional complex as well as the promoter. A set of proteins known as coregulators also interact with the receptors to regulate gene expression. However, ligands are not the only mechanism through which receptors can regulate genes. When a ligand binds to its receptor, it alters the receptor activity and thus the expression of entire gene networks. Nuclear receptors have the ability to enhance or repress the expression of a gene in response to changes in the environment or to endocrine signals. NHRs are involved in a wide spectrum of functions and are key components of a great number of signaling pathways. Some receptors also include a COOH-terminal region (F) that aids in the folding of the receptor into a transcriptionally active form. Finally, there is a conserved region with LBD (E) that contains the activation function AF-2. The most variable and unique sequence of NHRs is the linker region (D), which aids in the conformational changes of the binding ligands. The second zinc finger contains a D-box, which mediates receptor dimerization. ![]() A P-box region is found on the first zinc finger and functions to recognize the half-site of a response element. In addition, the DNA-binding domain is composed of two zinc fingers and is the most conserved region of the NHR. ![]() A conserved DNA-binding domain (C) binds to specific DNA sequences known as the hormone response element (HREs). Modifying the A/B domain produces different isoforms of the receptors. The variable NH 2 terminal (A/B) contains an activation function AF-1 domain, and the AF-2 domain is found in the E domain also known as the ligand-binding domain (LBD). There are two activation function (AF) domains that bind to DNA. While being involved in a wide range of functions, NHRs have very conserved structure of functional domains ( Fig. 1, 2 The goal of this review is to discuss the role of NHRs in the development of the CNS, with an emphasis on their function in the brain and the eye and their impact on human disease. NHRs modulate numerous processes, such as central nervous system (CNS) development, homeostasis, reproduction, differentiation, metabolism, circadian functions, steroidogenesis, cell differentiation, and lipid metabolism. NHRs share a common structure characterized by dimeric zinc fingers that can bind to a lipid-soluble hormone and form a complex with other proteins, such as cofactors and histones, to regulate gene expression. NHRs are activated by ligands, such as hormones and vitamins, and a subset of these NHRs fall under the category of orphan receptors with unidentified ligands. These receptors belong to a large family of genes that regulate gene expression. The nuclear hormone receptor (NHR) superfamily is a group of transcriptional regulators that play a key role in numerous pathways, including development, growth, metabolism, and maintenance.
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