Transcriptional noise
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Transcriptional noise is a primary cause of the variability (noise) in gene expression occurring between cells in isogenic populations (see also cellular noise) .{{cite journal |pmid=18957198 |year=2008 |last1=Raj |first1=A |last2=Van Oudenaarden |first2=A |title=Nature, nurture, or chance: stochastic gene expression and its consequences |volume=135 |issue=2 |pages=216–26 |doi=10.1016/j.cell.2008.09.050 |journal=Cell |pmc=3118044}} A proposed source of transcriptional noise is transcriptional bursting{{cite journal |pmid=16360033 |year=2005 |last1=Golding |first1=I |last2=Paulsson |first2=J |last3=Zawilski |first3=SM |last4=Cox |first4=EC |title=Real-time kinetics of gene activity in individual bacteria |volume=123 |issue=6 |pages=1025–36 |doi=10.1016/j.cell.2005.09.031 |journal=Cell|doi-access=free }}{{cite journal |pmid=16713960 |year=2006 |last1=Chubb |first1=JR |last2=Trcek |first2=T |last3=Shenoy |first3=SM |last4=Singer |first4=RH |title=Transcriptional pulsing of a developmental gene |volume=16 |issue=10 |pages=1018–25 |doi=10.1016/j.cub.2006.03.092 |journal=Current Biology|pmc=4764056 |bibcode=2006CBio...16.1018C }}{{cite journal |pmid=17048983 |year=2006 |last1=Raj |first1=A |last2=Peskin |first2=CS |last3=Tranchina |first3=D |last4=Vargas |first4=DY |last5=Tyagi |first5=S |title=Stochastic mRNA synthesis in mammalian cells |volume=4 |issue=10 |pages=e309 |doi=10.1371/journal.pbio.0040309 |pmc=1563489 |journal=PLOS Biology |doi-access=free }} although other sources of heterogeneity, such as unequal separation of cell contents at mitosis are also likely to contribute considerably.{{Cite journal
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| doi = 10.1038/ng.729
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| journal = Nature Genetics
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| year = 2010
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}} Bursting transcription, as opposed to simple probabilistic models of transcription, reflects multiple states of gene activity, with fluctuations between states separated by irregular intervals, generating uneven protein expression between cells. Noise in gene expression can have tremendous consequences on cell behaviour, and must be mitigated or integrated. In certain contexts, such as establishment of viral latency, the survival of microbes in rapidly changing stressful environments, or several types of scattered differentiation, the variability may be essential.{{Cite journal
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| title = Stochastic gene expression in a lentiviral positive-feedback loop: HIV-1 Tat fluctuations drive phenotypic diversity
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| year = 2005
| pmid = 16051143
| arxiv = q-bio/0608002
| s2cid = 8061716
| doi = 10.1126/science.1147888
| pmid = 18388284
| year = 2008
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|bibcode = 2008Sci...320...65L }} Variability also impacts upon the effectiveness of clinical treatment, with resistance of bacteria and yeast to antibiotics demonstrably caused by non-genetic differences.{{Cite journal
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| pmc =
}}{{cite journal |last1=Blake |first1=William J |last2=Balázsi |first2=Gábor |last3=Kohanski |first3=Michael A |last4= Isaacs |first4= Farren J |last5= Murphy |first5= Kevin F |last6= Kuang |first6= Yina |last7= Cantor |first7= Charles R |last8= Walt |first8= David R |last9= Collins |first9= James J |date=2006 |title=Phenotypic Consequences of Promoter-Mediated Transcriptional Noise |journal=Molecular Cell |volume=24 |issue=6 |pages=853–865 |doi= 10.1016/j.molcel.2006.11.003|pmid=17189188 |doi-access=free }} Variability in gene expression may also contribute to resistance of sub-populations of cancer cells to chemotherapy {{Cite journal
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| last16 = Settleman | first16 = J.
| title = A chromatin-mediated reversible drug tolerant state in cancer cell subpopulations
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| journal = Cell
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| year = 2010
| pmc = 2851638
| pmid = 20371346
}} and appears to be a barrier to curing HIV.{{Cite journal
| last1 = Weinberger | first1 = A. D.
| last2 = Weinberger | first2 = L. S.
| title = Stochastic fate selection in HIV-infected patients
| doi = 10.1016/j.cell.2013.09.039
| journal = Cell
| volume = 155
| issue = 3
| pages = 497–9
| year = 2013
| pmid = 24243007
| doi-access = free
}}