Chromatin rearrangements in development
Introduction
Chromatin, the complex of DNA, proteins and RNA present in nuclei of eukaryotes, serves to organize and compact the genetic material. Additionally, chromatin must retain the flexibility to make genetic information accessible when needed, and therefore, the degree of compaction has to be tightly regulated. This regulation involves methylation of DNA and histone modifications, often summarized as the ‘histone code’ (reviewed in references [1, 2]). DNA and histone modifications recruit various non-histone proteins to specific chromosomal regions [3, 4] and eventually create a defined nuclear structure, which can be studied by cytogenetic and molecular means.
Historically, DNA staining provided the basis for a cytological distinction between weakly stained euchromatin, now known to be gene-rich, and brightly stained heterochromatin, which usually contains various repetitive sequences [5]. Molecular markers have also served to define heterochromatin and euchromatin, but such markers often are more ambiguous than previously thought. For example, even the classical heterochromatin markers Heterochromatin Protein 1 (HP1) and histone 3 lysine 9 trimethylation have now been found in euchromatin [6, 7, 8].
In plants, chromatin structure is best understood in Arabidopsis thaliana. Its interphase nuclear architecture is very concise because its small genome contains only ∼15% highly repetitive sequences, which are compacted into well-defined heterochromatic spots [9, 10]. Repetitive sequences and heterochromatically silenced genes aggregate to form the chromocenters from which chromosomal gene-rich euchromatic regions emanate as loops [11] (Figure 1). This subnuclear architecture is altered in some mutants with defective chromatin formation and dynamics. Mutations in genes such as DECREASE IN DNA METHYLATION1 (DDM1), a chromatin remodeling factor required for maintenance of DNA methylation, or the maintenance DNA methyltransferase MET1, greatly impair chromocenter formation [12, 13]. 5-methyl cytosine, which normally colocalizes with chromocenters, is dispersed, histone modifications are redistributed, centromeric repeats are decondensed and silent transposons are reactivated [12, 13, 14, 15]. By contrast, defective DNA methylation in the chromomethylase3 mutant does not dramatically change overall nuclear architecture [16]. Similar to ddm1 and met1, mutants that disrupt the CHROMATIN ASSEMBLY FACTOR (CAF)-1, which functions in DNA replication-dependent nucleosome deposition [17], can still form chromocenters but these contain less DNA [18]. In mammals, CAF-1 is specifically required for heterochromatin organization in pluripotent embryonic cells [19].
During development, chromatin needs to be altered and restructured, and mutants with defective chromatin dynamics often suffer from abnormalities at multiple developmental stages (e.g. reference [20]). There are several recent reviews discussing the proteins required for chromatin dynamics during plant development [21, 22, 23, 24]. Here, we will focus on the changes in chromatin structure during development.
Section snippets
Cell dedifferentiation coincides with large-scale chromatin decondensation
Differentiated cells have characteristic gene expression patterns and corresponding well-defined chromosomal chromatin states; changes of the differentiation status require restructuring of the chromatin. In animals, embryonic stem cells have little heterochromatin, and global remodeling and compaction of chromatin structure occurs during differentiation (reviewed in reference [25]). Similarly, chromatin unfolding is an early step of cellular dedifferentiation [25, 26].
In plants,
Development is accompanied by global changes in nuclear architecture
Establishment of nuclear architecture during cell differentiation has been studied during seedling development and leaf maturation in Arabidopsis thaliana: Initially, heterochromatin is not fully developed, but chromocenters increase in size with the age of the leaf (Figure 2). Concomitantly, transcription from repeats, that is, minor 5S rDNA, gradually ceases [34]. Interestingly, nuclei from two-day-old leaves of both wild-type and ddm1 mutants have a similar heterochromatin content of 6% and
Local chromatin rearrangements accompany changes in gene expression
Not all chromatin rearrangements during development are global—often chromatin states are changed only locally. Root hair formation involves expression of GLABRA2 (GL2) specifically in files of atrichoblasts that alternate with files of hair-forming trichoblasts. In cells with active GL2, the GL2 region exists in a relaxed chromatin conformation, while in cells with silent GL2, this region exists in a compact conformation [43]. If an atypical cell division replaces a trichoblast into an
Environmental cues can remodel chromatin structure to control development
Vernalization is the acceleration of flowering by exposure to prolonged periods of cold, and is a well-studied example of a developmental transition controlled by the environment that requires chromatin remodeling at specific loci (reviewed in references [44, 45]). In Arabidopsis, vernalization is largely mediated by repression of the floral repressor FLOWERING LOCUS C (FLC). Lasting cold transiently activates VERNALIZATION-INSENSITIVE 3 (VIN3), which mediates the initial repression of FLC [46
Distribution in space: what do histone modifications reveal?
Recently, genome-wide profiling technologies entered plant developmental biology [53]. On the chromatin level, chromatin and 5-methyl cytosine immunoprecipitation coupled to microarrays (ChIP-chip and m-chip) are most prominent technologies. DNA-tiling arrays were used to study DNA methylation in Arabidopsis [54•, 55]. One surprising finding was that DNA methylation was not only restricted to promoters of silent genes as previously believed but was also prominent in the coding region of active
Conclusions
Previously, developmental biology often focused on the action of individual transcriptional regulators and their target genes. Here, we discussed that new results show that chromatin and nuclear architecture change both, locally and globally during development. On a local scale, histone modifications are changed to allow reliable maintenance and propagation of transcriptional states during the cell cycle. On a global scale, packaging and intranuclear targeting of DNA changes. So far, research
References and recommended reading
Papers of particular interest, published within the period of review, have been highlighted as:
• of special interest
•• of outstanding interest
Acknowledgements
We thank Claudia Köhler, Cristina Alexandre and Yvonne Steinbach for critical reading of the manuscript. Work in the authors’ laboratory is supported by SNF project 3100AO-116060 and ETH project TH-16/05-2. We apologize for not citing all the relevant papers of our colleagues owing to space constraints.
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