In plants, seasonal changes in day length are perceived in leaves, which initiate long-distance signaling that induces flowering at the shoot apex. The identity of the long-distance signal has yet to be determined. In Arabidopsis , activation of FLOWERING LOCUS T ( FT ) transcription in leaf vascular tissue (phloem) induces flowering. We found that FT messenger RNA is required only transiently in the leaf. In addition, FT fusion proteins expressed specifically in phloem cells move to the apex and move long distances between grafted plants. Finally, we provide evidence that FT does not activate an intermediate messenger in leaves. We conclude that FT protein acts as a long-distance signal that induces Arabidopsis flowering.

Like many species, the model plant Arabidopsis thaliana exhibits multiple different life histories in natural environments. We grew mutants impaired in different signaling pathways in field experiments across the species' native European range in order to dissect the mechanisms underlying this variation. Unexpectedly, mutational loss at loci implicated in the cold requirement for flowering had little effect on life history except in late-summer cohorts. A genetically informed photothermal model of progression toward flowering explained most of the observed variation and predicted an abrupt transition from autumn flowering to spring flowering in late-summer germinants. Environmental signals control the timing of this transition, creating a critical window of acute sensitivity to genetic and climatic change that may be common for seasonally regulated life history traits.

Smyd3 is a protein methyltransferase implicated in cancer development. Here we show that Smyd3 expression in mice is required for chemically induced liver and colon cancer formation. In these organs Smyd3 functions in the nucleus, stimulating the transcription of several key regulators involved in cell proliferation, epithelial-mesenchymal transition, the JAK/Stat3 oncogenic pathway, as well as the Myc and Ctnnb1 oncogenes. Smyd3 interacts with H3K4Me3-modified histone tails, which facilitates its recruitment to the core promoter regions of most active genes. Smyd3 binding density on target genes positively correlates with increased RNA polymerase-II density and transcriptional outputs. Despite its widespread distribution, the transcription-potentiating function of Smyd3 is restricted to a particular set of genes, whose expression is induced specifically during carcinogenesis.

Daily rhythms of gene expression provide a benefit to most organisms by ensuring that biological processes are activated at the optimal time of day. Although temporal patterns of expression control plant traits of agricultural importance, how natural genetic variation modifies these patterns during the day and how precisely these patterns influence phenotypes is poorly understood. The circadian clock regulates the timing of gene expression, and natural variation in circadian rhythms has been described, but circadian rhythms are measured in artificial continuous conditions that do not reflect the complexity of biologically relevant day/ night cycles. By studying transcriptional rhythms of the eveningexpressed gene GIGANTEA (GI) at high temporal resolution and during day/night cycles, we show that natural variation in the timing of GI expression occurs mostly under long days in 77 Arabidopsis accessions. This variation is explained by natural alleles that alter light sensitivity of GI, specifically in the evening, and that act at least partly independent of circadian rhythms. Natural alleles induce precise changes in the temporal waveform of GI expression, and these changes have detectable effects on PHYTOCHROME INTERACTING FACTOR 4 expression and growth. Our findings provide a paradigm for how natural alleles act within day/night cycles to precisely modify temporal gene expression waveforms and cause phenotypic diversity. Such alleles could confer an advantage by adjusting the activity of temporally regulated processes without severely disrupting the circadian system. diurnal | circadian | rhythms | Arabidopsis | GIGANTEA

The canonical Wnt pathway plays a central role in stem cell maintenance, differentiation, and proliferation in the intestinal epithelium. Constitutive, aberrant activity of the TCF4/β-catenin transcriptional complex is the primary transforming factor in colorectal cancer. We identify a nuclear long non-coding RNA, termed WiNTRLINC1, as a direct target of TCF4/β-catenin in colorectal cancer cells. WiNTRLINC1 positively regulates the expression of its genomic neighbor ASCL2, a transcription factor that controls intestinal stem cell fate. WiNTRLINC1 interacts with TCF4/β-catenin to mediate the juxtaposition of its promoter with the regulatory regions of ASCL2. ASCL2, in turn, regulates WiNTRLINC1 transcriptionally, closing a feedforward regulatory loop that controls stem cell-related gene expression. This regulatory circuitry is highly amplified in colorectal cancer and correlates with increased metastatic potential and decreased patient survival. Our results uncover the interplay between non-coding RNA-mediated regulation and Wnt signaling and point to the diagnostic and therapeutic potential of WiNTRLINC1.

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During the last decade, high-throughput sequencing efforts in the fields of transcriptomics and epigenomics have shed light on the noncoding part of the transcriptome and its potential role in human disease. Regulatory noncoding RNAs are broadly divided into short and long noncoding transcripts. The latter, also known as lncRNAs, are defined as transcripts longer than 200 nucleotides with low or no protein-coding potential. LncRNAs form a diverse group of transcripts that regulate vital cellular functions through interactions with proteins, chromatin, and even RNA itself. Notably, an important regulatory aspect of these RNA species is their association with the epigenetic machinery and the recruitment of its regulatory apparatus to specific loci, resulting in DNA methylation and/or post-translational modifications of histones. Such epigenetic modifications play a pivotal role in maintaining the active or inactive transcriptional state of chromatin and are crucial regulators of normal cellular development and tissue-specific gene expression. Evidently, aberrant expression of lncRNAs that interact with epigenetic modifiers can cause severe epigenetic disruption and is thus is closely associated with altered gene function, cellular dysregulation, and malignant transformation. Here, we survey the latest breakthroughs concerning the role of lncRNAs interacting with the epigenetic machinery in various forms of cancer.

Seasonal variability in environmental parameters such as day length regulates many aspects of plant development. The transition from vegetative growth to flowering in Arabidopsis is regulated by seasonal changes in day length through a genetically defined molecular cascade known as the photoperiod pathway. Recent advances were made in understanding the tissues in which different components of the photoperiod pathway act to regulate floral induction. These studies highlighted the key role of the FT protein, which is produced in the leaves in response to inductive day lengths and traffics through the phloem to initiate flowering at the shoot apex. Unveiling the cellular and molecular details of this systemic signaling process will be required for a complete understanding of flowering regulation and other photoperiodic processes. IntroductionIn many plants flowering is induced only on exposure to appropriate environments. Day length and temperature are the most important of these environmental signals, providing seasonal cues that enable varieties of a species to become adapted to life at particular latitudes or altitudes. Flower development occurs at the shoot apical meristem or in lateral meristems, but these are often covered in growing leaves so that their exposure to light is limited. Thus, it is, perhaps, not surprising that day length should be perceived in the leaves, as these evolved to maximize light perception for photosynthesis. The spatial separation between the organs that perceive light and those in which floral development occurs raises issues of the mechanisms by which the floral signal is communicated between organs of the plant. Recently, work in Arabidopsis provided evidence that the small FLOWERING LOCUS T (FT) protein is at least a component of this signal, and work in other species strengthened this conclusion. These results were reviewed at length during the last year [1,2]. Here, we briefly summarize the molecular-genetic data and give emphasis to papers that appeared most recently, as well as to the questions of cell biology that arise from current models. Pathways that regulate flowering in the leafArabidopsis flowers early under long days characteristic of summer and late under short winter days. Isolation of lateflowering mutants of Arabidopsis that are insensitive to day length, flowering at similar times under long and short days, provided access to genes that regulate flowering in response to photoperiod [1,2]. These genes comprise a regulatory pathway often referred to as the photoperiodic flowering pathway or long-day pathway. The mRNA of two of the genes in this pathway, FT and its close homolog TWIN SISTER OF FT (TSF), are expressed under long days but not short days [3][4][5]. The FT and TSF proteins belong to the CETS family, named after the three founding members, CENTRORADIALIS, TERMINAL FLOWER, and SELF PRUNING [6], and strongly promote flowering [3,7,5]. The mechanisms that lead to FT activation specifically under long days involve transcriptional and post-transcriptional ...