ReviewCombinatorial epigenetics, “junk DNA”, and the evolution of complex organisms
Section snippets
Some conditions under which “junk DNA” may help generate higher organisms
Genomes need to possess at least the following six basic properties (Table 1) if any sequences considered as “junk DNA” are to intervene in organismic evolution, as directly linked to the evolution of genes (leaving aside chromosomal evolution).
First, the distinction between genetic and epigenetic effects must apply. The existence of epigenetic effects is not episodic; it is at the core of living systems. The roles in chromatin of the polynucleotides and their interacting factors are
Degrees of specificity of regulatory effects originating in “junk DNA”
A general way for “junk DNA” to intervene in gene regulation no doubt depends on the capacity of this DNA to affect the balance of bound and free regulatory factors. Transcription factors extensively bind to non-protein-coding sequences (Cawley et al., 2004), either in functionally neutral associations, though often leading to perhaps functionally nonneutral local transcription of noncoding RNAs, or with effects on genome structure endowed with functional implications. In particular, factor
Junk DNA-dependent teleregulation of chromatin structure via spreading of chromatin modifications in cis
Regarding the question of the role that “junk DNA” located in the region of particular genes may play as originators of changes in transcriptional regulation, let us first consider effects in cis. We presume that, not infrequently, in some points of the genome, and within non-protein-coding DNA, a new chromatin structure is formed and is communicated to other points of the genome. The local nidus formation from which a new structure can spread or an old one can be selected for greater
Teleregulation of chromatin structure via spreading of chromatin modifications in trans
Indeed, another class of phenomena that might lead to teleregulatory effects relies on “gene clustering” or “gene kissing” processes, whereby genomic elements sharing sequence homology or analogous molecular regulatory complementary structural features meet in the three-dimensional space of the cell nucleus. Upon mutation of one interacting partner (that we may designate as “donor” locus), a change in chromatin structure may thus be communicated to the “acceptor” locus in contact with the
Wider implications of combinatorial epimutations
Selectable inheritable combinations of epigenetic changes in the transcription rate of individual genes can presumably be maintained in cells or organisms over a certain window of numbers of generations. That window can be of sufficient width to permit much rarer specific mutations with equivalent effects to occur and to be selected. These specific mutations would be of high penetrance and stability. They would produce the “assimilation” of certain constellations of epigenetic transmutations.
Acknowledgements
E.Z. was supported through the Institute of Molecular Medical Sciences by the Sylvia Robb Charitable Trust. G.C. was supported by grants from the Centre National de la Recherche Scientifique, the Human Frontier Science Program Organization, the European Union FP 6 (Network of Excellence “The Epigenome” and STREP “3D Genome”), the Ministère de la Recherche (ACI BCMS 2004), the Agence Nationale de la Recherche, and by the Association pour la Recherche sur le Cancer.
References (119)
- et al.
Specific protection of methylated CpGs in mammalian nuclei
Cell
(1989) Misunderstandings about isochores
Gene
(2001)- et al.
Association of transcriptionally silent genes with Ikaros complexes at centromeric heterochromatin
Cell
(1997) - et al.
Dynamic repositioning of genes in the nucleus of lymphocytes preparing for cell division
Mol. Cell
(1999) - et al.
Chromo-domain proteins: linking chromatin structure to epigenetic regulation
Curr. Opin. Cell Biol.
(1998) Unbiased mapping of transcription factor binding sites along human chromosomes 21 and 22 points to widespread regulation of noncoding RNAs
Cell
(2004)- et al.
Does looping and clustering in the nucleus regulate gene expression?
Curr. Opin. Cell Biol.
(2004) - et al.
Chromosome evolution in eukaryotes: a multi-kingdom perspective
Trends Genet.
(2005) Perturbation of nuclear architecture by long-distance chromosome interactions
Cell
(1996)Expression patterns and gene distribution in the human genome
Gene
(2002)
Expansions of transgene repeats cause heterochromatin formation and gene silencing in Drosophila
Cell
RNAi components are required for nuclear clustering of Polycomb group response elements
Cell
Histone variants, nucleosome assembly and epigenetic inheritance
Trends Genet.
Allele-specific gene expression uncovered
Trends Genet.
HS2 enhancer function is blocked by a transcriptional terminator inserted between the enhancer and the promoter
J. Biol. Chem.
The HS2 enhancer of the beta-globin locus control region initiates synthesis of non-coding, polyadenylated RNAs independent of a cis-linked globin promoter
J. Mol. Biol.
Transposable elements are found in a large number of human protein-coding genes
Trends Genet.
A role for TFIIIC transcription factor complex in genome organization
Cell
Epigenetic inheritance, genetic assimilation and speciation
J. Theor. Biol.
The value-added genome: building and maintaining genomic cytosine methylation landscapes
Curr. Opin. Genet. Dev.
Epigenetic codes for heterochromatin formation and silencing: rounding up the usual suspects
Cell
Epigenetic inheritance in the mouse
Curr. Biol.
Signaling network model of chromatin
Cell
Inheritance of allelic blueprints for methylation patterns
Cell
Gene-specific targeting of H3K9 methylation is sufficient for initiating repression in vivo
Curr. Biol.
Assembly of silent chromatin during thymocyte development
Semin. Immunol.
The establishment and maintenance of DNA methylation patterns in mouse somatic cells
Semin. Cancer Biol.
Widely separated multiple transgene integration sites in wheat chromosomes are brought together at interphase
Plant J.
Evolution. Reducible complexity
Science
The SINE-encoded mouse B2 RNA represses mRNA transcription in response to heat shock
Nat. Struct. Mol. Biol.
SINE retroposons can be used in vivo as nucleation centers for de novo methylation
Mol. Cell. Biol.
Transient colocalization of X-inactivation centres accompanies the initiation of X inactivation
Nat. Cell Biol.
Inheritance of Polycomb-dependent chromosomal interactions in Drosophila
Genes Dev.
Structural and Evolutionary Genomics
Intermingling of chromosome territories in interphase suggests role in translocations and transcription-dependent associations
PLoS Biol.
Cis-acting variation in the expression of a high proportion of genes in human brain
Hum. Genet.
Genetic dissection of transcriptional regulation in budding yeast
Science
Evolution of hormone–receptor complexity by molecular exploitation
Science
Coregulated human globin genes are frequently in spatial proximity when active
J. Cell Biol.
The insulation of genes from external enhancers and silencing chromatin
Proc. Natl. Acad. Sci. U. S. A.
Role of histone H3 lysine 27 methylation in Polycomb-group silencing
Science
Selection for short introns in highly expressed genes
Nat. Genet.
Natural variation in human gene expression assessed in lymphoblastoid cells
Nat. Genet.
Detection of regulatory variation in mouse genes
Nat. Genet.
Genetic modification of heterochromatic association and nuclear organisation in Drosophila
Nature
Large-scale chromosomal movements during interphase progression in Drosophila
J. Cell Biol.
Invention et Finalité en Biologie
The Origin of Species
Transgene repeat arrays interact with distant heterochromatin and cause silencing in cis and trans
Genetics
Transvection effects in Drosophila
Annu. Rev. Genet.
Cited by (42)
Human repetitive sequence densities are mostly negatively correlated with R/Y-based nucleosome-positioning motifs and positively correlated with W/S-based motifs
2013, GenomicsCitation Excerpt :Second, when multiple sequence measures are pairwisely correlated, the cause-effect relationship between these measures intrinsically affect conditional correlation result [50]. The idea that repetitive sequences have relevant evolutionary impact on higher organisms only under certain conditions was discussed in ref. [51]. Whether the correlation between NPM and repetitive sequence densities discussed here can disappear by conditionaling on other sequence measures worth future studies.
MicroRNA in the regulation and expression of serotonergic transmission in the brain and other tissues
2011, Current Opinion in PharmacologyCitation Excerpt :Once integrated into regulatory networks, miRNAs show striking evolutionary conservation, and the continual generation of new forms drives phylogenic innovation, variation and even speciation [10]. MiRNA sequences are mainly located in inter-genic regions between protein-coding sequences, underpinning arguments that the vast ‘dark matter’ expanse of non-coding DNA is of considerable regulatory importance—and should be considered as anything other than evolutionary ‘junk’ [11,12]. Nonetheless, certain miRNAs are contained in the introns – and probably exons – of protein-coding genes [13•].
Epigenetics in adaptive evolution and development: The interplay between evolving species and epigenetic mechanisms
2011, Handbook of EpigeneticsEpigenetics in Adaptive Evolution and Development: The Interplay Between Evolving Species and Epigenetic Mechanisms
2010, Handbook of Epigenetics: The New Molecular and Medical GeneticsFunctional nuclear architecture studied by microscopy: Present and future
2010, International Review of Cell and Molecular BiologyCitation Excerpt :Considering the possible role of gene repositioning for gene regulation, one should not forget the importance of local fluctuations of unfolding chromatin with respect to the availability of genes to transcription machineries (Sato et al., 2004). Of particular interest are hints that a long-range spatial nuclear convergence of genes, which are located many megabases apart on the same chromosome or even on different chromosomes, might be involved in mechanisms of gene activation or silencing (Bartkuhn and Renkawitz, 2008; Zuckerkandl and Cavalli, 2007). This phenomenon has been referred to as “gene kissing” (Cavalli, 2007; Kioussis, 2005).
A Role for the MS Analysis of Nucleic Acids in the Post-Genomics Age
2010, Journal of the American Society for Mass SpectrometryCitation Excerpt :Once upon a time dismissed as “selfish” or “junk DNA” [67, 68], the intragenic (i.e., intronic) and intergenic sequences representing the vast majority of the transcribed pool are now undergoing extensive re-evaluation. Indeed, the last decade has witnessed resurgent interest in the elucidation of the functions of noncoding elements (ncRNA) [69–71]. Although new classes of functional RNA are being discovered on a regular basis, their total amount still does not account for the entire transcribed pool [72].