The Chemistry of Regulation of Genes and Other Things

Ptashne, Mark

doi:10.1074/jbc.x114.547323

Cited by 40 publications

(27 citation statements)

References 98 publications

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“…In several cases, such maintained expression has been explicitly shown to be mediated by direct autoregulation, the simplest form of a classic feedback loop 11, 14, 4748 . For example, the LIM homeobox TF mec–3 (the “M” in LIM domain) autoregulates in C. elegans touch sensory neurons, which require mec–3 for their terminal differentiation 49 , the Zn finger TFs che–1 and odr–7 autoregulate in the C.elegans ASE and AWA sensory neurons, respectively 11, 50 , in which they initiate the respective differentiation programs and the LIM homeobox TF ttx–3 and the Prd–type homeobox TF ceh–10 jointly autoregulate their expression in the cholinergic AIY interneurons, aside from initiating the terminal differentiation program of AIY 14 .…”

Section: Autoregulationmentioning

confidence: 99%

Maintenance of postmitotic neuronal cell identity

2014

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The identity of specific cell types in the nervous system is defined by the expression of neuron type–specific gene batteries. How the expression of such batteries is initiated during nervous system development has been under intensive study over the past few decades. However, comparatively little is known about how gene batteries that define the terminally differentiated state of a neuron type are maintained throughout the life of an animal. We provide here an overview of studies in invertebrate and vertebrate model systems that have carved out the general and not commonly appreciated principle that neuronal identity is maintained in postmitotic neurons by the sustained, and often autoregulated expression of the same transcription factors that have initiated terminal differentiation in a developing organism. Disruption of postmitotic maintenance mechanisms may result in neuropsychiatric and neurodegenerative conditions.

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Section: Autoregulationmentioning

confidence: 99%

Maintenance of postmitotic neuronal cell identity

2014

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“…What can it mean to say that DNA methylation is repressive when activation of a gene removes methylation (e.g., Bird 2002;Nagae et al 2011;Hackett et al 2012;Qian et al 2012;Gan et al 2013;Xie et al 2013;Bestor et al 2014)? The search for the mechanism of semiconservative histone modifications continues (Deal et al 2010;Xu et al 2010;Nakano et al 2011;Tran et al 2012;Whitehouse and Smith 2013) despite evidence that the modifications respond to expression state rather than control it (Kilpinen et al 2013;Ptashne 2014;Teves et al 2014). It's not that histone modification and DNA methylation are not correlated with gene expression differences-they are-but the possibility that they may be responsive rather than causal has not been disproved (Henikoff 2005;Ptashne 2013).…”

Section: The Clarificationmentioning

confidence: 99%

What Do You Mean, “Epigenetic”?

2015

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Interest in the field of epigenetics has increased rapidly over the last decade, with the term becoming more identifiable in biomedical research, scientific fields outside of the molecular sciences, such as ecology and physiology, and even mainstream culture. It has become increasingly clear, however, that different investigators ascribe different definitions to the term. Some employ epigenetics to explain changes in gene expression, others use it to refer to transgenerational effects and/or inherited expression states. This disagreement on a clear definition has made communication difficult, synthesis of epigenetic research across fields nearly impossible, and has in many ways biased methodologies and interpretations. This article discusses the history behind the multitude of definitions that have been employed since the conception of epigenetics, analyzes the components of these definitions, and offers solutions for clarifying the field and mitigating the problems that have arisen due to these definitional ambiguities.

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“…This paradigm has provided a powerful unifying mechanism for transcription, validated by a large amount of experimental evidence over the last five decades (see, e.g., ref. 2). Further evidence of the power of TFs to act as master regulators of gene expression and cell identity is illustrated by their ability to reprogram differentiated fibroblasts into embryonic stem (ES) cells (3).…”

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confidence: 99%

Transcription factor binding predicts histone modifications in human cell lines

Benveniste

Sonntag

Sanguinetti

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

112

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Gene expression in higher organisms is thought to be regulated by a complex network of transcription factor binding and chromatin modifications, yet the relative importance of these two factors remains a matter of debate. Here, we show that a computational approach allows surprisingly accurate prediction of histone modifications solely from knowledge of transcription factor binding both at promoters and at potential distal regulatory elements. This accuracy significantly and substantially exceeds what could be achieved by using DNA sequence as an input feature. Remarkably, we show that transcription factor binding enables strikingly accurate predictions across different cell lines. Analysis of the relative importance of specific transcription factors as predictors of specific histone marks recapitulated known interactions between transcription factors and histone modifiers. Our results demonstrate that reported associations between histone marks and gene expression may be indirect effects caused by interactions between transcription factors and histone-modifying complexes.epigenetics | gene regulation G ene expression is the fundamental process through which genetic information is dynamically and specifically deployed within cells. It is, therefore, of vital importance to all organisms and tightly controlled at both the transcriptional and posttranscriptional levels. Consequently, the elucidation of generegulatory mechanisms has been a central focus of biological research, with the area of transcriptional regulation having attracted intense attention over the last four decades.The canonical players in transcriptional regulation are sequence-specific DNA-binding transcription factors (TFs) that modulate gene expression by facilitating or inhibiting the recruitment of RNA polymerase to gene promoters (1). This paradigm has provided a powerful unifying mechanism for transcription, validated by a large amount of experimental evidence over the last five decades (see, e.g., ref. 2). Further evidence of the power of TFs to act as master regulators of gene expression and cell identity is illustrated by their ability to reprogram differentiated fibroblasts into embryonic stem (ES) cells (3).Research in the field of epigenetics has, however, suggested an alternative view that places posttranslational modifications of the histone subunits of nucleosomes in a central role of transcriptional regulation. The finding that particular combinations of histone modifications are associated with active and repressed gene promoters (4) has led to suggestions that a histone code controls gene expression (5, 6). Support for this hypothesis has come from the recent application of bioinformatic approaches to whole-genome measurements of both histone modifications and gene expression, which have demonstrated that gene expression can be predicted from histone modifications (7,8). This model has generated intense interest and is part of the stimulation behind the search for epigenetic causes of human disease (9).However, although histone mo...

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The Chemistry of Regulation of Genes and Other Things

Cited by 40 publications

References 98 publications

Maintenance of postmitotic neuronal cell identity

Maintenance of postmitotic neuronal cell identity

What Do You Mean, “Epigenetic”?

Transcription factor binding predicts histone modifications in human cell lines

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