Thinking quantitatively about transcriptional regulation (original) (raw)
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Transcriptional Regulation: Molecules, Involved Mechanisms, and Misregulation
International Journal of Molecular Sciences, 2019
Transcriptional regulation is a critical biological process that allows the cell or an organism to respond to a variety of intra- and extra-cellular signals, to define cell identity during development, to maintain it throughout its lifetime, and to coordinate cellular activity [...]
RNA polymerase: the vehicle of transcription
Trends in Microbiology, 2008
Glossary cAMP: cyclic adenosine monophosphate. CAP: catabolite activator protein. F(bridge)-helix and G(trigger)-loop: mobile elements of the RNAP catalytic center (sometimes also called 'bridge helix' and 'trigger loop', respectively). i+1: the substrate binding site in the RNAP catalytic center. P lac : promoter of the lactose operon. ppGpp: guanosine tetraphosphate, the effector of the stringent response. RNAP: RNA polymerase. RPc: RNAP-promoter closed complex. RPitc: RNAP-promoter initial transcribing complex. RPo: RNAP-promoter open complex. aCTD: carboxy-terminal domain of alpha subunit. s1, s2, s3, s4: evolutionarily conserved domains of s 70 . s3-s4 linker: sigma subunit linker element connecting domains s3 and s4. s 54 : sigma N, the sigma factor regulating nitrogen metabolism. s 70 : sigma 70, the housekeeping sigma factor in Escherichia coli.
Malleable machines take shape in eukaryotic transcriptional regulation
Nature Chemical Biology, 2008
Transcriptional control requires the spatially and temporally coordinated action of many macromolecular complexes. Chromosomal proteins, transcription factors, co-activators and components of the general transcription machinery, including RNA polymerases, often use structurally or stoichiometrically ill-defined regions for interactions that convey regulatory information in processes ranging from chromatin remodeling to mRNA processing. Determining the functional significance of intrinsically disordered protein regions and developing conceptual models of their action will help to illuminate their key role in transcription regulation. Complexes comprising disordered regions often display short recognition elements embedded in flexible and sequentially variable environments that can lead to structural and functional malleability. This provides versatility to recognize multiple targets having different structures, facilitate conformational rearrangements and physically communicate with many partners in response to environmental changes. All these features expand the capacities of ordered complexes and give rise to efficient regulatory mechanisms.
Journal of Chemistry and Nutritional Biochemistry, 2021
The non-coding elements that control transcription are found in the chromatin structure of organisms. Recent findings identify the non-coding regulatory elements (e.g., enhancers, silencers, promoters) that control transcription and examine their respective protein interactions. The multiple topological environment limitations, including interactions of promoter-enhancer and specific enhancer-bound proteins with variable promoter compatibility, begin to shape a picture. These transcription factors and co-factors contribute to various expressions based on which enhancers and promoters are found inside sequences. A novel trait of transcription factors and co-factors establishes nuclear microenvironments or membranes compartments with phase-separated liquid characteristics. These settings are capable of enriching some proteins and tiny molecules at the expense of others. To better understand gene regulation
Genome architecture and the role of transcription
Current Opinion in Cell Biology, 2010
During development or in response to environmental stimuli, eukaryotic genes change both their expression and position in 3D nuclear space. Then, is a gene transcribed because of its position, or is position determined by transcription? Are genes stochastically or deterministically engaged in transcription cycles? Recent results confirm that RNA polymerases and their transcription factors play central roles in genome organization, and that stochastic events can give rise to apparently deterministic expression. As is so often the case in biology, structure both determines function and is influenced by it.
Structural basis of transcription activation
Science (New York, N.Y.), 2016
Class II transcription activators function by binding to a DNA site overlapping a core promoter and stimulating isomerization of an initial RNA polymerase (RNAP)-promoter closed complex into a catalytically competent RNAP-promoter open complex. Here, we report a 4.4 angstrom crystal structure of an intact bacterial class II transcription activation complex. The structure comprises Thermus thermophilus transcription activator protein TTHB099 (TAP) [homolog of Escherichia coli catabolite activator protein (CAP)], T. thermophilus RNAP σ(A) holoenzyme, a class II TAP-dependent promoter, and a ribotetranucleotide primer. The structure reveals the interactions between RNAP holoenzyme and DNA responsible for transcription initiation and reveals the interactions between TAP and RNAP holoenzyme responsible for transcription activation. The structure indicates that TAP stimulates isomerization through simple, adhesive, stabilizing protein-protein interactions with RNAP holoenzyme.