Structural biology of shelterin and telomeric chromatin: the pieces and an unfinished puzzle.

The six-subunit shelterin complex binds to mammalian telomeres and protects them from triggering multiple DNA damage response pathways. The loss of this protective function by shelterin can have detrimental effects on cells. In this review, we first discuss structural studies of shelterin, detailing the contributions of each subunit and inter-subunit interactions in protecting chromosome ends.

Molecular basis of chromatin remodelling by DDM1 involved in plant DNA methylation.

Eukaryotic gene regulation occurs at the chromatin level, which requires changing the chromatin structure by a group of ATP-dependent DNA translocases-namely, the chromatin remodellers. In plants, chromatin remodellers function in various biological processes and possess both conserved and plant-specific components. DECREASE IN DNA METHYLATION 1 (DDM1) is a plant chromatin remodeller that plays a key role in the maintenance DNA methylation.

Molecular mechanisms of the RNA polymerases in plant RNA-directed DNA methylation.

In plants, two atypical DNA-dependent RNA polymerases, RNA polymerase IV (Pol IV) and Pol V, and an RNA-DEPENDENT RNA POLYMERASE 2 (RDR2) together produce noncoding RNAs (ncRNAs) to guide the plant-specific RNA-directed DNA methylation (RdDM). Although both Pol IV and Pol V have evolved from the canonical Pol II, they have adapted to different roles in RdDM. The mechanisms of their adaptation are key to understanding plant DNA methylation and the divergent evolution of polymerases.

Structural basis of telomeric nucleosome recognition by shelterin factor TRF1.

Shelterin and nucleosomes are the key players that organize mammalian chromosome ends into the protective telomere caps. However, how they interact with each other at telomeres remains unknown. We report cryo-electron microscopy structures of a human telomeric nucleosome both unbound and bound to the shelterin factor TRF1.

Structure and mechanism of the plant RNA polymerase V.

In addition to the conserved RNA polymerases I to III (Pols I to III) in eukaryotes, two atypical polymerases, Pols IV and V, specifically produce noncoding RNA in the RNA-directed DNA methylation pathway in plants. Here, we report on the structures of cauliflower Pol V in the free and elongation conformations. A conserved tyrosine residue of NRPE2 stacks with a double-stranded DNA branch of the transcription bubble to potentially attenuate elongation by inducing transcription stalling.

Structure and mechanism of histone methylation dynamics in Arabidopsis.

Histone methylation plays a central role in regulating chromatin state and gene expression in Arabidopsis and is involved in a variety of physiological and developmental processes. Dynamic regulation of histone methylation relies on both histone methyltransferase "writer" and histone demethylases "eraser" proteins. In this review, we focus on the four major histone methylation modifications in Arabidopsis H3, H3K4, H3K9, H3K27, and H3K36, and summarize current knowledge of the dynamic regulation of these modifications, with an emphasis on the biochemical and structural perspectives of histone methyltransferases and demethylases.

TEM1 combinatorially binds to and recruits a Polycomb factor to repress the floral transition in .

TEMPRANILLO 1 (TEM1) is a transcriptional repressor that participates in multiple flowering pathways and negatively regulates the juvenile-to-adult transition and the flowering transition. To understand the molecular basis for the site-specific regulation of () by TEM1, we determined the structures of the two plant-specific DNA-binding domains in TEM1, AP2 and B3, in complex with their target DNA sequences from the gene 5'-untranslated region (5'-UTR), revealing the molecular basis for TEM1 specificity for its DNA targets. In vitro binding assays revealed that the combination of the AP2 and B3 binding sites greatly enhanced the overall binding of TEM1 to the 5'-UTR, indicating TEM1 combinatorically recognizes the gene 5'-UTR.

Binding of guide piRNA triggers methylation of the unstructured N-terminal region of Aub leading to assembly of the piRNA amplification complex.

PIWI proteins use guide piRNAs to repress selfish genomic elements, protecting the genomic integrity of gametes and ensuring the fertility of animal species. Efficient transposon repression depends on amplification of piRNA guides in the ping-pong cycle, which in Drosophila entails tight cooperation between two PIWI proteins, Aub and Ago3. Here we show that post-translational modification, symmetric dimethylarginine (sDMA), of Aub is essential for piRNA biogenesis, transposon silencing and fertility.

Structural insights into the multivalent binding of the Arabidopsis FLOWERING LOCUS T promoter by the CO-NF-Y master transcription factor complex.

Flowering plants sense various environmental and endogenous signals to trigger the floral transition and start the reproductive growth cycle. CONSTANS (CO) is a master transcription factor in the photoperiod floral pathway that integrates upstream signals and activates the florigen gene FLOWERING LOCUS T (FT). Here, we performed comprehensive structural and biochemical analyses to study the molecular mechanism underlying the regulation of FT by CO in Arabidopsis thaliana.

Embryonic resetting of the parental vernalized state by two B3 domain transcription factors in Arabidopsis.

Some overwintering plants acquire competence to flower, after experiencing prolonged cold in winter, through a process termed vernalization. In the crucifer plant Arabidopsis thaliana, prolonged cold induces chromatin-mediated silencing of the potent floral repressor FLOWERING LOCUS C (FLC) by Polycomb proteins. This vernalized state is epigenetically maintained or 'memorized' in warm rendering plants competent to flower in spring, but is reset in the next generation.

The Arabidopsis H3K27me3 demethylase JUMONJI 13 is a temperature and photoperiod dependent flowering repressor.

In plants, flowering time is controlled by environmental signals such as day-length and temperature, which regulate the floral pathway integrators, including FLOWERING LOCUS T (FT), by genetic and epigenetic mechanisms. Here, we identify an H3K27me3 demethylase, JUMONJI 13 (JMJ13), which regulates flowering time in Arabidopsis. Structural characterization of the JMJ13 catalytic domain in complex with its substrate peptide reveals that H3K27me3 is specifically recognized through hydrogen bonding and hydrophobic interactions.

Structure of the Arabidopsis JMJ14-H3K4me3 Complex Provides Insight into the Substrate Specificity of KDM5 Subfamily Histone Demethylases.

In chromatin, histone methylation affects the epigenetic regulation of multiple processes in animals and plants and is modulated by the activities of histone methyltransferases and histone demethylases. The jumonji domain-containing histone demethylases have diverse functions and can be classified into several subfamilies. In humans, the jumonji domain-containing Lysine (K)-Specific Demethylase 5/Jumonji and ARID Domain Protein (KDM5/JARID) subfamily demethylases are specific for histone 3 lysine 4 trimethylation (H3K4me3) and are important drug targets for cancer treatment.