Orchestrated response: a symphony of transcription factors for gene control.

By B. Lemon, R. Tjian. Genes & Development, 2000

837 citations recorded by the source corpus.

An enormous body of work generated over the past three decades has revealed that eukaryotic gene transcription is a remarkably intricate biochemical process that is tightly regulated at many levels. Biochemical and genetic analysis of various model organisms has identified an astounding number of protein factors responsible for transcriptional control. Although a large assortment of gene-specific DNA-binding regulators was somewhat anticipated, the sheer complexity of the general machinery relative to prokaryotes has been a surprise. Even more unexpected were the numerous and intricate layers of control imposed by the diversification of co-activators and co-repressors, some of which possess enzymatic activities. Many interactions between the identified factors and some of their rate-limiting steps have been discerned. Despite these advances, surprisingly little is known about the detailed mechanisms by which individual genes are turned on or off in a cell. Recent evidence suggests that there is an ordered progression of events leading to RNA synthesis in vivo and that a highly structured eukaryotic nucleus may be important in orchestrating transcription. In this review, we present our interpretation of recent findings and discuss various models that integrate these observations with the emerging elaborate molecular apparatus that has evolved to control gene expression. Eukaryotic cells carry a tremendous amount of genetic information just to encode the 6000 to 100,000 proteins necessary to perpetuate life from yeast to animals. In addition, genomes must also contain vast amounts of cis-regulatory DNA responsible for directing spatial and temporal patterns of gene expression in response to metabolic requirements, developmental programs, and a plethora of external stimuli. To maintain and control such a large genetic load, eukaryotes have organized colinear DNA into discrete chromosomes each packaged into chromatin, the minimal unit of which has been defined as the nucleosome (Kornberg 1974; Luger et al. 1997). Variable degrees of DNA sequence accessibility exist within chromatin throughout the cell cycle to accommodate essential biological processes such as DNA replication, gene expression, and cell division. However, classically held notions of chromatin as merely a passive DNA-packaging vehicle and global repressor of transcription have proven to be inadequate to explain its role in gene expression (Lorch et al. 1987; for review, see Grunstein 1992). Instead, it has become clear that chromatin is a dynamic and active participant in regulating transcription of the eukaryotic genome. Thus, the question of how gene expression is regulated in complex eukaryotic genomes has re-focused on the molecular machines that have evolved to navigate through chromatin and mediate transcriptional control.

Subfields: Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/0e3cdf33ed212838b653d83a50d0e122a1e8cd73

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Citations in the corpus

AnimalTFDB: a comprehensive animal transcription factor database (2011, background): “In this regulation, transcriptional regulatory system plays a key role and involves diverse proteins, including RNA polymerase, basal and sequence specific DNA-binding transcription factors (TFs), transcription cofactors and chromatin remodeling proteins (1).”
A census of human transcription factors: function, expression and evolution (2009, background): “In addition, a host of sequence-specific DNA-binding TFs direct transcription initiation to specific promoter”
Structure‐based prediction of transcription factor binding sites using a protein‐DNA docking approach (2008, background): “8 These computational techniques are generally designed to solve two related issues: (1) For a given set of sequences that harbor the binding sites of a particular TF, find the location of the sites; and (2) For a given set of known binding sites, develop a representation of their binding signature,”
Targets of AtWRKY6 regulation during plant senescence and pathogen defense. (2002, background): “In plants, as in other organisms, many developmental processes and responses to different stress stimuli underlay complex regulatory mechanisms operating at the level of gene expression (Lemon and Tjian 2000).”
Targeted recruitment of Set1 histone methylase by elongating Pol II provides a localized mark and memory of recent transcriptional activity. (2003, background): “…residues are tar- merase II (Pol II) is a complex process (Conaway et al., geted to active promoters (Milne et al., 2002; Nakamura 2000; Lemon and Tjian, 2000; Orphanides and Reinberg, 2000; Naar et al., 2001) that is linked to subsequent events of mRNA production including capping,…”
The RNA polymerase II core promoter: a key component in the regulation of gene expression. (2002, background): “By complex formulae that have yet to be solved, the expression of each of these thousands of genes is controlled by a wide variety of mechanisms (e.g., see Lefstin and Yamamoto 1998; Roeder 1998; Struhl 1999; Glass and Rosenfeld 2000; Lee and Young 2000; Lemon and Tjian 2000; Strahl and Allis 2000; ”
Androgen receptor (AR) coregulators: an overview. (2002, background): “In this model, a dynamic association between coactivator holocomplexes mediating chromatin modification or recruitment of the basal transcription factors occurs with the DNAbound receptor to allow transcription from the target gene (29, 137).”
The evolution of transcriptional regulation in eukaryotes. (2003, background): “…Xmk2 and CKDN2X within the teleost genus Xiphophorus (reviewed in Orr and Presgraves 2000); and a promoter polymorphism in desaturase 2 of D. melanogaster that is correlated with intraspecific differences in mating behavior and may be involved in premating isolation (Fang, Takahashi, and Wu 2002).”
The General Transcription Machinery and General Cofactors (2006, background): “Indeed, evidence supporting both models has been reported for different regulatory systems (Orphanides et al., 1996; Hampsey, 1998; Parvin and Young, 1998; Lee and Young, 2000; Lemon and Tjian, 2000).”
Computational analysis of core promoters in the Drosophila genome (2002, background): “Background Transcription initiation is one of the most important control points in regulating gene expression [1,2].”