Featured
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Letter |
Phosphorylation of histone H3T6 by PKCβI controls demethylation at histone H3K4
The amino-terminal tails of histone proteins are subject to a variety of post-translational modifications; addition or removal of these 'marks' facilitates gene activation or silencing. Here, a mechanism is defined that modulates the activity of the dual-specificity histone demethylase LSD1 during androgen-dependent transcription. Androgen-dependent signalling through protein kinase C beta I leads to phosphorylation of a histone amino acid, which prevents demethylation of an adjacent amino acid by LSD1.
- Eric Metzger
- , Axel Imhof
- & Roland Schüle
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News & Views |
An avian sexual revolution
Hormones are not all-powerful in determining whether birds develop with male or female features. Chickens that are genetic sexual mosaics reveal that individual cells also have a say in the matter.
- Lindsey A. Barske
- & Blanche Capel
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Letter |
Control of female gamete formation by a small RNA pathway in Arabidopsis
Female gametes in flowering plants develop from a meiotic division of a precursor cell followed by mitotic divisions of one of the resulting haploid cells to yield the gametophyte. Here, ARGONAUTE 9 (AGO9) — a protein involved in RNA interference — is identified as a factor required for specification of the gametophyte. AGO9 is found not in the cell destined to be the gametophyte, but in the neighbouring companion cells, suggesting that it functions in a non-cell-autonomous manner.
- Vianey Olmedo-Monfil
- , Noé Durán-Figueroa
- & Jean-Philippe Vielle-Calzada
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Letter |
Transcription-independent ARF regulation in oncogenic stress-mediated p53 responses
In response to oncogenic stress, the tumour suppressor ARF activates the p53 protein. ARF protein is highly stable in most human cell lines, so it has been thought that ARF activation occurs mainly at the level of transcription. Here, however, ARF is shown to be unstable in normal human cells but stable in cancer cells, through a transcription-independent mechanism. A ubiquitin ligase for ARF is identified and shown to promote ARF degradation in normal cells. This activity is prevented in cancer cells, stabilizing ARF.
- Delin Chen
- , Jing Shan
- & Wei Gu
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Letter |
Transcriptional control of preadipocyte determination by Zfp423
An understanding of how fat cells (adipocytes) develop will contribute to our understanding of obesity. The differentiation of committed preadipocytes into adipocytes is known to be controlled by PPARγ and several other transcription factors. But what turns a cell into a preadipocyte? Here, the zinc-finger protein Zfp423 is identified as a transcriptional regulator of preadipocyte determination.
- Rana K. Gupta
- , Zoltan Arany
- & Bruce M. Spiegelman
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Research Highlights |
Cell biology: Lost in the mail
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Letter |
Compensatory evolution in mitochondrial tRNAs navigates valleys of low fitness
Evolution from one fitness peak to another must involve either transitions through intermediates of low fitness or skirting round the fitness valley through compensatory mutations elsewhere. Here, the base pairs in mitochondrial tRNA stems is used as a model to show that deep fitness valleys can be traversed. Transitions between AU and GC pairs have occurred during mammalian evolution without help from genetic drift or mutations elsewhere.
- Margarita V. Meer
- , Alexey S. Kondrashov
- & Fyodor A. Kondrashov
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Letter |
Proviral silencing in embryonic stem cells requires the histone methyltransferase ESET
Endogenous retroviruses (ERVs) are widely dispersed in mammalian genomes, and are silenced in somatic cells by DNA methylation. Here, an ERV silencing pathway independent of DNA methylation is shown to operate in embryonic stem cells. The pathway involves the histone H3K9 methyltransferase ESET and might be important for ERV silencing during the stages in embryogenesis when DNA methylation is reprogrammed.
- Toshiyuki Matsui
- , Danny Leung
- & Yoichi Shinkai
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Letter |
Encoding multiple unnatural amino acids via evolution of a quadruplet-decoding ribosome
Although new amino acids with desirable properties can be devised, only a few have been successfully introduced into proteins by the cellular machinery. Even then, only one type of unnatural amino acid can be added to a given protein. Here, a new system has been designed that could allow the incorporation of up to 200 novel amino acids. The system involves an orthogonal ribosome that uses quadruplet — rather than triplet — codons, as well as orthogonal tRNA synthetase–tRNA pairs.
- Heinz Neumann
- , Kaihang Wang
- & Jason W. Chin
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Letter |
Multiple native states reveal persistent ruggedness of an RNA folding landscape
The 'thermodynamic hypothesis' proposes that the sequence of a biological macromolecule defines its folded, active structure as a global energy minimum in the folding landscape; however, it is not clear whether there is only one global minimum or several local minima corresponding to active conformations. Here, using single-molecule experiments, an RNA enzyme is shown to fold into multiple distinct native states that interconvert.
- Sergey V. Solomatin
- , Max Greenfeld
- & Daniel Herschlag
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Research Highlights |
Biochemistry: Chemical gene switch
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Letter |
Ancient animal microRNAs and the evolution of tissue identity
Recent work suggests that microRNAs might have been important in the evolution of complexity in multicellular animals. Here it is shown that the most ancient known microRNA, miR–100, was initially active in neurosecretory cells around the mouth. Other highly conserved varieties were first present in specific tissues and organ systems. Thus, microRNA expression was initially restricted to an ancient set of ancient animal cell types and tissues.
- Foteini Christodoulou
- , Florian Raible
- & Detlev Arendt
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Review Article |
Expansion of the eukaryotic proteome by alternative splicing
- Timothy W. Nilsen
- & Brenton R. Graveley
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Letter |
Genome-wide erasure of DNA methylation in mouse primordial germ cells is affected by AID deficiency
The extent of epigenetic reprogramming in mammalian primordial germ cells (PGCs) and in early embryos, and its molecular mechanisms, are poorly understood. DNA methylation profiling in PGCs now reveals a genome–wide erasure of methylation, with female PGCs being less methylated than male ones. A deficiency of the cytidine deaminase AID interferes with the genome–wide erasure of DNA methylation, indicating that AID has a critical function in epigenetic reprogramming.
- Christian Popp
- , Wendy Dean
- & Wolf Reik
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Letter |
Transcriptional role of cyclin D1 in development revealed by a genetic–proteomic screen
Although cyclin D1 is frequently overexpressed in human cancers, the full range of its functions in normal development and oncogenesis is unclear. Here, tagged cyclin D1 knock-in mouse strains are developed to allow a search for cyclin D1-binding proteins in different mouse organs using high-throughput mass spectrometry. The results show that, in addition to its established cell cycle roles, cyclin D1 has an in vivo transcriptional function in mouse development.
- Frédéric Bienvenu
- , Siwanon Jirawatnotai
- & Piotr Sicinski
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Letter |
DNMT1 maintains progenitor function in self-renewing somatic tissue
Progenitor cells sustain the capacity of self-renewing tissues for proliferation while suppressing cell cycle exit and terminal differentiation. DNA methylation is one potential epigenetic mechanism for the cellular memory needed to preserve the somatic progenitor state through cell divisions. The DNA methyltransferase 1 and other regulators of DNA methylation are now shown to be essential for epidermal progenitor cell function.
- George L. Sen
- , Jason A. Reuter
- & Paul A. Khavari
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Letter |
KAP1 controls endogenous retroviruses in embryonic stem cells
Much of the mammalian genome is derived from retroelements, a significant proportion of which are endogenous retroviruses (ERVs). ERVs are transcriptionally silenced during early embryogenesis by histone and DNA methylation, but the initiators of this process are largely unknown. Here, deletion of KAP1 is shown to lead to a marked upregulation of a range of ERVs in mouse embryonic stem cells and in early embryos.
- Helen M. Rowe
- , Johan Jakobsson
- & Didier Trono
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Letter |
JARID2 regulates binding of the Polycomb repressive complex 2 to target genes in ES cells
Polycomb proteins have a key role in regulating the expression of genes essential for development, differentiation and maintenance of cell fates. Here, Polycomb repressive complex 2 (PRC2) is shown to form a complex with JARID2, a Jumonji domain protein. JARID2 is required for the binding of Polycomb proteins to target genes in embryonic stem cells as well as for the proper differentiation of ES cells.
- Diego Pasini
- , Paul A. C. Cloos
- & Kristian Helin
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Letter |
An allosteric mechanism of Rho-dependent transcription termination
Rho is a general transcription termination factor in bacteria, but the mechanism by which it disrupts the RNA polymerase (RNAP) elongation complex is unknown. Here, Rho is shown to bind tightly to the RNAP throughout the transcription cycle, with the formation of the RNAP–Rho complex being crucial for termination. Furthermore, RNAP is proposed to have an active role in Rho termination through an allosteric mechanism.
- Vitaly Epshtein
- , Dipak Dutta
- & Evgeny Nudler
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Letter |
Chimpanzee and human Y chromosomes are remarkably divergent in structure and gene content
Little is known about the recent evolution of the Y chromosome because only the human Y chromosome has been fully sequenced. The sequencing of the male-specific region of the Y chromosome (MSY) in the chimpanzee and comparison between the MSYs of the two species now reveals that they differ radically in sequence structure and gene content, indicating rapid evolution over the past 6 million years.
- Jennifer F. Hughes
- , Helen Skaletsky
- & David C. Page
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Letter |
Hsp90 prevents phenotypic variation by suppressing the mutagenic activity of transposons
Phenotypic robustness in the face of genetic and environmental perturbations — known as canalization — relies on buffering mechanisms. Hsp90 chaperone machinery has been proposed to be an evolutionarily conserved buffering mechanism of phenotypic variance. Here, an additional, perhaps alternative, mechanism whereby Hsp90 influences phenotypic variation is proposed; Hsp90 mutations can generate new variation by transposon-mediated mutagenesis.
- Valeria Specchia
- , Lucia Piacentini
- & Maria P. Bozzetti
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Article |
Opposing microRNA families regulate self-renewal in mouse embryonic stem cells
The differentiation of an embryonic stem cell (ESC) requires both suppression of the self-renewal process and activation of the specific differentiation pathway. The let-7 family of microRNAs (miRNAs) are now shown to suppress the self-renewal program in cells that are normally unable to silence this program, whereas introduction of ESC cell cycle regulating miRNAs blocks the action of let-7. Thus, the interplay between these two groups of miRNAs dictates cell fate.
- Collin Melton
- , Robert L. Judson
- & Robert Blelloch
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