LINE Retrotransposon RNA Is an Essential Structural and Functional Epigenetic Component of a Core Neocentromeric Chromatin

Chüeh, Anderly C.; Northrop, Emma L.; Brettingham-Moore, Kate H.; Choo, K.H. Andy; Wong, Lee H.

doi:10.1371/journal.pgen.1000354

Cited by 149 publications

(129 citation statements)

References 54 publications

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“…This is consistent with studies of the role of transcription and RNAi in centromere activity in S. pombe (Volpe et al, 2002(Volpe et al, , 2003Chen et al, 2008); however, the role for transcription in metazoan kinetochore activity has been little studied (Saffery et al, 2003;Fukagawa et al, 2004;Wong et al, 2007;Chueh et al, 2009). Our previous studies found that alphoid tetO kinetochore inactivation by the tTS correlated with the recruitment of heterochromatin protein HP1␣ and that direct recruitment of HP1␣ as a TetR:EYFP fusion protein could also inactivate the kinetochore (Nakano et al, 2008).…”

Section: Molecular Biology Of the Cell 4200supporting

confidence: 89%

Hierarchical Inactivation of a Synthetic Human Kinetochore by a Chromatin Modifier

Cardinale

Bergmann

Kelly

et al. 2009

MBoC

114

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We previously used a human artificial chromosome (HAC) with a synthetic kinetochore that could be targeted with chromatin modifiers fused to tetracycline repressor to show that targeting of the transcriptional repressor tTS within kinetochore chromatin disrupts kinetochore structure and function. Here we show that the transcriptional corepressor KAP1, a downstream effector of the tTS, can also inactivate the kinetochore. The disruption of kinetochore structure by KAP1 subdomains does not simply result from loss of centromeric CENP-A nucleosomes. Instead it reflects a hierarchical disruption of the outer kinetochore, with CENP-C levels falling before CENP-A levels and, in certain instances, CENP-H being lost more readily than CENP-C. These results suggest that this novel approach to kinetochore dissection may reveal new patterns of protein interactions within the kinetochore. INTRODUCTIONThe centromere/kinetochore is one of the most complex cellular substructures, with more than 80 protein components described to date (reviewed in Carroll and Straight, 2006;Cheeseman and Desai, 2008;Fukagawa, 2008;Vagnarelli et al., 2008). These components perform the complex job of attaching chromosomes to the mitotic spindle; ensuring that those attachments are correct; signaling to delay mitotic progression if they are not, and regulating the movements of the chromosomes toward the spindle poles in anaphase.The kinetochore is assembled at a unique locus on each natural chromosome. However, for organisms with regional centromeres (Pluta et al., 1995), this reflects only a preference¤, and not an absolute requirement for particular DNA sequences. Kinetochores can form on a wide range of singlecopy and repeated DNA sequences, leading to the conclusion that the ultimate determinants of kinetochore assembly are epigenetic. The long-term purpose of our studies is to determine the epigenetic "landscape" that promotes kinetochore assembly and its maintenance during cell divisions.Experiments including yeast genetics, RNA interference (RNAi) studies in mammalian cells, and gene knockout analysis in mouse and chicken DT40 cells have revealed that kinetochores assemble on a foundation of specialized chromatin containing the kinetochore-specific histone H3 variant CENP-A (Earnshaw and Rothfield, 1985). CENP-A is upstream of almost all other known components in the kinetochore assembly pathway. However, that pathway is multiplex, as recent studies in chicken and Drosophila show that inner kinetochore proteins CENP-H and -C are required for normal CENP-A loading or retention (Okada et al., 2006;Goshima et al., 2007;Erhardt et al., 2008).Our work was inspired by an approach first developed a number of years ago in which cloned fragments of human centromeric DNA were used to form human artificial chromosomes (HACs) in HT1080 fibrosarcoma cells (Harrington et al., 1997;Ikeno et al., 1998). Originally, HAC formation was only achieved with regular repeated arrays of ␣-satellite DNA containing CENP-B boxes Ohzeki et al., 2002;Okada et al., 2007)....

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Section: Molecular Biology Of the Cell 4200supporting

confidence: 89%

Hierarchical Inactivation of a Synthetic Human Kinetochore by a Chromatin Modifier

Cardinale

Bergmann

Kelly

et al. 2009

MBoC

114

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“…Centromeric satellite and retroelement transcripts have been identified in a multitude of different organisms, including rice, maize, beetle, tammar wallaby, mouse, and human, and are of various sizes, from 35 to 5,000 nt in length (Topp et al 2004;BouzinbaSegard et al 2006;Lee et al 2006;Yan et al 2006;Pezer and Ugarković 2008;Carone et al 2009;Chueh et al 2009;Ferri et al 2009;Du et al 2010). CT levels, like PCT levels, can change depending on developmental stage and tissue type.…”

Section: Centromeric Transcriptionmentioning

confidence: 99%

“…The specific function of each type of CT may be dependent on their size, with observed CTs associating with CENP-A ranging from 35 to >900 nt in length (Topp et al 2004;Chueh et al 2009;Ferri et al 2009;Du et al 2010). For example, the knockdown of a specific sized long interspersed nucleotide element (LINE), which is shown to interact with CENP-A at a human neocentromere, causes a decrease in CENP-A loading (Chueh et al 2009). CenH3 in maize was shown to interact with long CentC satellite transcripts (Du et al 2010).…”

Section: Centromeric Transcriptionmentioning

confidence: 99%

“…While we are gaining a better understanding of the pathway that results in the assembly of CENP-A nucleosomes at centromeres, the precise mechanism for determining the genomic location of CENP-A deposition is unknown. Recent work implicates centromeric transcripts as active participants in CENP-A deposition and centromere function, adding complexity to a pathway previously thought to be restricted to a large protein network (Topp et al 2004;Chueh et al 2009;Ferri et al 2009;Bergmann et al 2011Bergmann et al , 2012. Historically, centromeres were considered simply heterochromatin-rich and thus transcriptionally silent.…”

Section: Introductionmentioning

confidence: 99%

“…Interestingly, transcripts emanating from both the pericentromere and centromere core have been identified in a multitude of organisms (Eymery et al 2009a;Stimpson and Sullivan 2010). Moreover, recent studies have identified proteins that interact with these transcripts (Topp et al 2004;Wong et al 2007;Chueh et al 2009;Ferri et al 2009;Du et al 2010;Hsieh et al 2011), analyzed the effects of increased and decreased transcription on genome stability (Bergmann et al 2011;Ohkuni and Kitagawa 2011;Bergmann et al 2012), or identified changes in transcription in stressed or diseased cells (Eymery et al 2009b;Gopalakrishnan et al 2009;Ting et al 2011;Zhu et al 2011). In this review, we will present pericentric and centromeric noncoding RNA transcription and discuss its diverse roles in modified histone recruitment, centromere function and stability, and insulator activity as well as newly discovered correlations between centromere and pericentromere transcription and human disease.…”

Section: Introductionmentioning

confidence: 99%

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Pericentric and centromeric transcription: a perfect balance required

2012

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The pericentromere and centromere regions of the genome have previously been considered tightly compacted and transcriptionally inert. However, there is mounting evidence that these regions not only actively produce transcripts but that these pericentric and centromeric transcripts are also vital to maintaining genome stability and proper cell division. In this review, we define the pericentromere and centromere of eukaryotic chromosomes in terms of their histone modifications and their nascent transcripts. In addition, we present the currently known roles these transcripts play in heterochromatin formation, development, and differentiation, as well as their interaction with centromeric proteins, and ultimately centromere function. Recent work has added considerable complexity to the theoretical framework defining the innate requirement for pericentric and centromeric transcription. It is clear that maintaining a fine balance of transcriptional output is critical, as deviations from this balance result in centromere disfunction and genomic instability.

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The Evolution of CentromericDNASequences

Brown

O’Neill

2014

Encyclopedia of Life Sciences

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For most eukaryotic species, the centromere is comprised of millions of base pairs of tandemly repeated deoxyribonucleic acid (DNA) sequences. Centromere function is broadly conserved across eukaryotic phyla, yet centromere DNA presents several unique conundrums for biologists, further complicated by the challenges in studying highly repeated regions of complex genomes. Contrary to the expectation that centromeric sequences would be constrained to maintain centromere function across species, these sequences are among the most rapidly evolving sequences in any given genome. This discordance between functional constraint and sequence divergence, termed the ‘centromere paradox’, appears to defy basic laws of Mendelian inheritance. Multiple genetic mechanisms have been proposed to explain centromeric DNA complexity and rapid evolutionary divergence, taking into consideration the unique chromosome architecture and dynamics of the centromere during both mitosis and meiosis. Stochastic processes affecting sequence evolution and the selective constraint necessary for centromere protein recognition are balanced in an ongoing conflict that ultimately manifests as rapid centromere DNA evolution. Key Concepts: Loss of centromere function does not equate to loss of centromere sequence. Conversely, centromere sequences do not strictly demarcate a functional centromere. The constitution of centromeric satellite DNAs across species differs not only in sequence, but also in the repeat unit length, abundance of the repeat unit and the complexity of the genomic structure of multiple repeat units. The more commonly found regional centromere is typified by a distinct, linear organisation of a given satellite repeat unit into high‐copy tandem repeats of that unit than can span megabases of DNA. The high homology of the higher‐order satellite repeats within a centromere is consistent with their function to effectively bind centromere proteins, wherein selection may favour homogeneity to retain centromere function. Initial forms of an active centromere do not necessarily require HOR satellite arrays, but rather such arrays evolve over evolutionary timescales following stable establishment and inheritance of a new centromere. The process of molecular drive, involving concerted evolution and gene conversion results in the homogenisation and fixation of a given repeat variant and may lead to the convergent and concerted evolution of satellites within one species. Genetic conflict and/or meiotic drive may be responsible for the different centromere satellite sequence suites found between species. Centromere Drive may be responsible for the rapid divergence of functional centromeric sequences between species. The coding sequences for two centromere proteins, CENP‐A (centromere‐specific histone H3) and CENP‐C (a centromere‐specific DNA binding protein), evolve at rates faster than expected for either neutral (unconstrained) or purifying (selectively constrained) evolution in many species. Mobile elements can impact the rate at which satellites are derived, expand, contract and homogenise within a species.

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LINE Retrotransposon RNA Is an Essential Structural and Functional Epigenetic Component of a Core Neocentromeric Chromatin

Cited by 149 publications

References 54 publications

Hierarchical Inactivation of a Synthetic Human Kinetochore by a Chromatin Modifier

Hierarchical Inactivation of a Synthetic Human Kinetochore by a Chromatin Modifier

Pericentric and centromeric transcription: a perfect balance required

The Evolution of CentromericDNASequences

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