Abstract:
:Given the large amount of genome-wide data that have been collected during the last decades, a good understanding of how and why cells change during development, homeostasis, and disease might be expected. Unfortunately, the opposite is true; triggers that cause cellular state changes remain elusive, and the underlying molecular mechanisms are poorly understood. Although genes with the potential to influence cell states are known, the historic dependency on methods that manipulate gene expression outside the endogenous chromatin context has prevented us from understanding how cells organize, interpret, and protect cellular programs. Fortunately, recent methodological innovations are now providing options to answer these outstanding questions, by allowing to target and manipulate individual genomic and epigenomic loci. In particular, three experimental approaches are now feasible due to DNA targeting tools, namely, activation and/or repression of master transcription factors in their endogenous chromatin context; targeting transcription factors to endogenous, alternative, or inaccessible sites; and finally, functional manipulation of the chromatin context. In this article, we discuss the molecular basis of DNA targeting tools and review the potential of these new technologies before we summarize how these have already been used for the manipulation of cellular states and hypothesize about future applications.
journal_name
Physiol Revjournal_title
Physiological reviewsauthors
Breunig CT,Köferle A,Neuner AM,Wiesbeck MF,Baumann V,Stricker SHdoi
10.1152/physrev.00034.2019subject
Has Abstractpub_date
2021-01-01 00:00:00pages
177-211issue
1eissn
0031-9333issn
1522-1210journal_volume
101pub_type
杂志文章abstract::This review summarizes the receptor-mediated vascular activities of calcitonin gene-related peptide (CGRP) and the structurally related peptide adrenomedullin (AM). CGRP is a 37-amino acid neuropeptide, primarily released from sensory nerves, whilst AM is produced by stimulated vascular cells, and amylin is secreted f...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00037.2003
更新日期:2004-07-01 00:00:00
abstract::Chronic pain can occur after peripheral nerve injury, infection, or inflammation. Under such neuropathic pain conditions, sensory processing in the affected body region becomes grossly abnormal. Despite decades of research, currently available drugs largely fail to control such pain. This review explores the possibili...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00011.2002
更新日期:2002-10-01 00:00:00
abstract::Oligodendrocytes generate multiple layers of myelin membrane around axons of the central nervous system to enable fast and efficient nerve conduction. Until recently, saltatory nerve conduction was considered the only purpose of myelin, but it is now clear that myelin has more functions. In fact, myelinating oligodend...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00031.2018
更新日期:2019-07-01 00:00:00
abstract::NHE3 is the brush-border (BB) Na(+)/H(+) exchanger of small intestine, colon, and renal proximal tubule which is involved in large amounts of neutral Na(+) absorption. NHE3 is a highly regulated transporter, being both stimulated and inhibited by signaling that mimics the postprandial state. It also undergoes downregu...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00030.2006
更新日期:2007-07-01 00:00:00
abstract::Intrarenal autoregulatory mechanisms maintain renal blood flow (RBF) and glomerular filtration rate (GFR) independent of renal perfusion pressure (RPP) over a defined range (80-180 mmHg). Such autoregulation is mediated largely by the myogenic and the macula densa-tubuloglomerular feedback (MD-TGF) responses that regu...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00042.2012
更新日期:2015-04-01 00:00:00
abstract::Protein toxins such as ricin and Shiga toxin with intracellular targets have to be endocytosed and translocated to the cytosol to inhibit the protein synthesis and thereby kill the cell. Ricin is internalized by both clathrin-dependent and -independent endocytic mechanisms, whereas Shiga toxin seems to be taken up exc...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.1996.76.4.949
更新日期:1996-10-01 00:00:00
abstract::Cutaneous wound healing is a complex process involving blood clotting, inflammation, new tissue formation, and finally tissue remodeling. It is well described at the histological level, but the genes that regulate skin repair have only partially been identified. Many experimental and clinical studies have demonstrated...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.2003.83.3.835
更新日期:2003-07-01 00:00:00
abstract::Angiotensin (ANG) II is a powerful and phylogenetically widespread stimulus to thirst and sodium appetite. When it is injected directly into sensitive areas of the brain, it causes an immediate increase in water intake followed by a slower increase in NaCl intake. Drinking is vigorous, highly motivated, and rapidly co...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.1998.78.3.583
更新日期:1998-07-01 00:00:00
abstract::The minK gene encodes a protein of 130 amino acids that has a single transmembrane segment and is expressed in many tissues including heart, uterus, and kidney. When Xenopus oocytes are injected with minK mRNA, a very slowly activating voltage-dependent potassium current is induced in these cells. The induced channels...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.1997.77.3.627
更新日期:1997-07-01 00:00:00
abstract::Cardiac myocytes rapidly proliferate during fetal life but exit the cell cycle soon after birth in mammals. Although the extent to which adult cardiac myocytes are capable of cell cycle reentry is controversial and species-specific differences may exist, it appears that for the vast majority of adult cardiac myocytes ...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00032.2006
更新日期:2007-04-01 00:00:00
abstract::The past two decades have witnessed an explosive growth of knowledge regarding postischemic myocardial dysfunction or myocardial "stunning." The purpose of this review is to summarize current information regarding the pathophysiology and pathogenesis of this phenomenon. Myocardial stunning should not be regarded as a ...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.1999.79.2.609
更新日期:1999-04-01 00:00:00
abstract::Green fluorescent protein (GFP) from the jellyfish Aequorea victoria and its homologs from diverse marine animals are widely used as universal genetically encoded fluorescent labels. Many laboratories have focused their efforts on identification and development of fluorescent proteins with novel characteristics and en...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00038.2009
更新日期:2010-07-01 00:00:00
abstract::Propagation of excitation in the heart involves action potential (AP) generation by cardiac cells and its propagation in the multicellular tissue. AP conduction is the outcome of complex interactions between cellular electrical activity, electrical cell-to-cell communication, and the cardiac tissue structure. As shown...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00025.2003
更新日期:2004-04-01 00:00:00
abstract::Biosynthesis and Degradation of CFTR. Physiol. Rev. 79, Suppl.: S167-S173, 1999. - Many of the mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that cause cystic fibrosis interfere with the folding and biosynthetic processing of nascent CFTR molecules in the endoplasmic reticulum. Mutat...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.1999.79.1.S167
更新日期:1999-01-01 00:00:00
abstract::A careful review of several different organs shows that with the information available today the beginnings of the microlymphatics in the tissue consist of endothelialized tubes only. Lymphatic smooth muscle within the collecting lymphatics appears further downstream, in some organs only outside the parenchyma. This p...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.1990.70.4.987
更新日期:1990-10-01 00:00:00
abstract::The vertebrate control of locomotion involves all levels of the nervous system from cortex to the spinal cord. Here, we aim to cover all main aspects of this complex behavior, from the operation of the microcircuits in the spinal cord to the systems and behavioral levels and extend from mammalian locomotion to the bas...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00015.2019
更新日期:2020-01-01 00:00:00
abstract::The last 10 years have witnessed a surge of interest for the mechanisms underlying the acquisition and extinction of classically conditioned fear responses. In part, this results from the realization that abnormalities in fear learning mechanisms likely participate in the development and/or maintenance of human anxiet...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00037.2009
更新日期:2010-04-01 00:00:00
abstract::The classic concept of gastrointestinal endocrinology is that of a few peptides released to the circulation from endocrine cells, which are interspersed among other mucosal cells in the upper gastrointestinal tract. Today more than 30 peptide hormone genes are known to be expressed throughout the digestive tract, whic...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.1998.78.4.1087
更新日期:1998-10-01 00:00:00
abstract::The transepithelial movement of fluids, electrolytes, and larger molecules is achieved by the activity of a host of specialized transporting proteins, including enzymes, receptors, and channels, that are located on either the apical, basal, or lateral plasma membrane domains of epithelial cells. In the kidney as well ...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.1996.76.1.245
更新日期:1996-01-01 00:00:00
abstract::The microvascular endothelial cell monolayer localized at the critical interface between the blood and vessel wall has the vital functions of regulating tissue fluid balance and supplying the essential nutrients needed for the survival of the organism. The endothelial cell is an exquisite "sensor" that responds to div...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00012.2005
更新日期:2006-01-01 00:00:00
abstract::While transport processes for amino acids and glucose have long been known to be expressed in the luminal and abluminal membranes of the endothelium comprising the blood-brain and blood-retinal barriers, it is only within the last decades that endothelial and smooth muscle cells derived from peripheral vascular beds h...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00022.2002
更新日期:2003-01-01 00:00:00
abstract::The discovery of cannabinoid receptors and subsequent identification of their endogenous ligands (endocannabinoids) in early 1990s have greatly accelerated research on cannabinoid actions in the brain. Then, the discovery in 2001 that endocannabinoids mediate retrograde synaptic signaling has opened up a new era for c...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00019.2008
更新日期:2009-01-01 00:00:00
abstract::Up to 50% of cancer patients suffer from a progressive atrophy of adipose tissue and skeletal muscle, called cachexia, resulting in weight loss, a reduced quality of life, and a shortened survival time. Anorexia often accompanies cachexia, but appears not to be responsible for the tissue loss, particularly lean body m...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00016.2008
更新日期:2009-04-01 00:00:00
abstract::Heterotrimeric G proteins are key players in transmembrane signaling by coupling a huge variety of receptors to channel proteins, enzymes, and other effector molecules. Multiple subforms of G proteins together with receptors, effectors, and various regulatory proteins represent the components of a highly versatile sig...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00003.2005
更新日期:2005-10-01 00:00:00
abstract::Vascular smooth muscle cells (VSMC) exhibit several growth responses to agonists that regulate their function including proliferation (hyperplasia with an increase in cell number), hypertrophy (an increase in cell size without change in DNA content), endoreduplication (an increase in DNA content and usually size), and...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.2001.81.3.999
更新日期:2001-07-01 00:00:00
abstract::The distal tubule of the mammalian kidney, defined as the region between the macula densa and the collecting duct, is morphologically and functionally heterogeneous. This heterogeneity has stymied attempts to define functional properties of individual cell types and has led to controversy concerning mechanisms and reg...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.2000.80.1.277
更新日期:2000-01-01 00:00:00
abstract::In the last few years there has been a veritable explosion of knowledge about cyclic nucleotide phosphodiesterases. In particular, the accumulating data showing that there are a large number of different phosphodiesterase isozymes have triggered an equally large increase in interest about these enzymes. At least seven...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.1995.75.4.725
更新日期:1995-10-01 00:00:00
abstract::Mitogen-activated protein kinases (MAPK) are serine-threonine protein kinases that are activated by diverse stimuli ranging from cytokines, growth factors, neurotransmitters, hormones, cellular stress, and cell adherence. Mitogen-activated protein kinases are expressed in all eukaryotic cells. The basic assembly of MA...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.1999.79.1.143
更新日期:1999-01-01 00:00:00
abstract::Although vitamin A was recognized as an "anti-infective vitamin" over 90 years ago, the mechanism of how vitamin A regulates immunity is only beginning to be understood. Early studies which focused on the immune responses in vitamin A-deficient (VAD) animals clearly demonstrated compromised immunity and consequently i...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00032.2013
更新日期:2015-01-01 00:00:00
abstract::Traditionally the auditory system was considered a hard-wired sensory system; this view has been challenged in recent years in light of the plasticity of other sensory systems, particularly the visual and somatosensory systems. Practical experience in clinical audiology together with the use of prosthetic devices, suc...
journal_title:Physiological reviews
pub_type: 杂志文章,评审
doi:10.1152/physrev.00002.2002
更新日期:2002-07-01 00:00:00