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Dissecting transcriptional amplification by MYC
by
Batchelor, Eric
, Das, Subhendu K
, Chow, Carson C
, Guo, Chunhua
, Simons, S Stoney
, Levens, David
, Nie, Zuqin
in
Algorithms
/ Analysis
/ Animals
/ cancer
/ Cancer Biology
/ Cell Line
/ Computational and Systems Biology
/ DNA binding proteins
/ Experiments
/ Gene Amplification
/ Gene expression
/ general amplifier
/ Genetic aspects
/ Genomes
/ Genomics
/ Glucocorticoids
/ Humans
/ Hypotheses
/ Kinases
/ kinetic mechanism of action
/ Mathematical models
/ michaelis-menten kinetics
/ Mutation
/ MYC
/ Myc protein
/ Plasmids
/ Promoters
/ Proteins
/ Proto-Oncogene Proteins c-myc - genetics
/ Proto-Oncogene Proteins c-myc - metabolism
/ Rats
/ Statistical analysis
/ Synthetic biology
/ transcription
/ Transcription (Genetics)
/ Transcription factors
/ Transcription Factors - genetics
/ Transcription Factors - metabolism
/ Transcriptional Activation
2020
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Dissecting transcriptional amplification by MYC
by
Batchelor, Eric
, Das, Subhendu K
, Chow, Carson C
, Guo, Chunhua
, Simons, S Stoney
, Levens, David
, Nie, Zuqin
in
Algorithms
/ Analysis
/ Animals
/ cancer
/ Cancer Biology
/ Cell Line
/ Computational and Systems Biology
/ DNA binding proteins
/ Experiments
/ Gene Amplification
/ Gene expression
/ general amplifier
/ Genetic aspects
/ Genomes
/ Genomics
/ Glucocorticoids
/ Humans
/ Hypotheses
/ Kinases
/ kinetic mechanism of action
/ Mathematical models
/ michaelis-menten kinetics
/ Mutation
/ MYC
/ Myc protein
/ Plasmids
/ Promoters
/ Proteins
/ Proto-Oncogene Proteins c-myc - genetics
/ Proto-Oncogene Proteins c-myc - metabolism
/ Rats
/ Statistical analysis
/ Synthetic biology
/ transcription
/ Transcription (Genetics)
/ Transcription factors
/ Transcription Factors - genetics
/ Transcription Factors - metabolism
/ Transcriptional Activation
2020
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Dissecting transcriptional amplification by MYC
by
Batchelor, Eric
, Das, Subhendu K
, Chow, Carson C
, Guo, Chunhua
, Simons, S Stoney
, Levens, David
, Nie, Zuqin
in
Algorithms
/ Analysis
/ Animals
/ cancer
/ Cancer Biology
/ Cell Line
/ Computational and Systems Biology
/ DNA binding proteins
/ Experiments
/ Gene Amplification
/ Gene expression
/ general amplifier
/ Genetic aspects
/ Genomes
/ Genomics
/ Glucocorticoids
/ Humans
/ Hypotheses
/ Kinases
/ kinetic mechanism of action
/ Mathematical models
/ michaelis-menten kinetics
/ Mutation
/ MYC
/ Myc protein
/ Plasmids
/ Promoters
/ Proteins
/ Proto-Oncogene Proteins c-myc - genetics
/ Proto-Oncogene Proteins c-myc - metabolism
/ Rats
/ Statistical analysis
/ Synthetic biology
/ transcription
/ Transcription (Genetics)
/ Transcription factors
/ Transcription Factors - genetics
/ Transcription Factors - metabolism
/ Transcriptional Activation
2020
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Journal Article
Dissecting transcriptional amplification by MYC
2020
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Overview
Supraphysiological MYC levels are oncogenic. Originally considered a typical transcription factor recruited to E-boxes (CACGTG), another theory posits MYC a global amplifier increasing output at all active promoters. Both models rest on large-scale genome-wide ”-omics’. Because the assumptions, statistical parameter and model choice dictates the ‘-omic’ results, whether MYC is a general or specific transcription factor remains controversial. Therefore, an orthogonal series of experiments interrogated MYC’s effect on the expression of synthetic reporters. Dose-dependently, MYC increased output at minimal promoters with or without an E-box. Driving minimal promoters with exogenous (glucocorticoid receptor) or synthetic transcription factors made expression more MYC-responsive, effectively increasing MYC-amplifier gain. Mutations of conserved MYC-Box regions I and II impaired amplification, whereas MYC-box III mutations delivered higher reporter output indicating that MBIII limits over-amplification. Kinetic theory and experiments indicate that MYC activates at least two steps in the transcription-cycle to explain the non-linear amplification of transcription that is essential for global, supraphysiological transcription in cancer.
Publisher
eLife Science Publications, Ltd,eLife Sciences Publications Ltd,eLife Sciences Publications, Ltd
Subject
/ Analysis
/ Animals
/ cancer
/ Computational and Systems Biology
/ Genomes
/ Genomics
/ Humans
/ Kinases
/ Mutation
/ MYC
/ Plasmids
/ Proteins
/ Proto-Oncogene Proteins c-myc - genetics
/ Proto-Oncogene Proteins c-myc - metabolism
/ Rats
/ Transcription Factors - genetics
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