Centromere Silencing Mechanisms

McNulty, Shannon M.; Sullivan, Beth A.

doi:10.1007/978-3-319-58592-5_10

Cited by 9 publications

(5 citation statements)

References 106 publications

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“…1994 ), and RNA polymerase (Pol) I, whereas transcription at sequences that do not favorably adopt non-B-form structures could occur via RNA Pol II. In support of this model, Pol II transcription has been shown to occur at human centromeres ( Quenet and Dalal 2014 ; McNulty and Sullivan 2017 ) and to be functionally important in budding yeast centromeres ( Ohkuni and Kitagawa 2011 ). Pol I has similarly been suggested to be involved in human centromere function ( Wong et al.…”

Section: Discussionmentioning

confidence: 90%

Non-B-Form DNA Is Enriched at Centromeres

Kasinathan

Henikoff

2018

Molecular Biology and Evolution

132

152

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Animal and plant centromeres are embedded in repetitive “satellite” DNA, but are thought to be epigenetically specified. To define genetic characteristics of centromeres, we surveyed satellite DNA from diverse eukaryotes and identified variation in <10-bp dyad symmetries predicted to adopt non-B-form conformations. Organisms lacking centromeric dyad symmetries had binding sites for sequence-specific DNA-binding proteins with DNA-bending activity. For example, human and mouse centromeres are depleted for dyad symmetries, but are enriched for non-B-form DNA and are associated with binding sites for the conserved DNA-binding protein CENP-B, which is required for artificial centromere function but is paradoxically nonessential. We also detected dyad symmetries and predicted non-B-form DNA structures at neocentromeres, which form at ectopic loci. We propose that centromeres form at non-B-form DNA because of dyad symmetries or are strengthened by sequence-specific DNA binding proteins. This may resolve the CENP-B paradox and provide a general basis for centromere specification.

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Section: Discussionmentioning

confidence: 90%

Non-B-Form DNA Is Enriched at Centromeres

Kasinathan

Henikoff

2018

Molecular Biology and Evolution

132

152

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“…Transcription in the case of dyad-enriched satellites may also occur through recognition by the rDNA transcription factor UBF, which has cruciform-binding activity (Copenhaver, et al 1994), and RNA polymerase (Pol) I, whereas transcription at sequences that do not favorably adopt non-B structures could occur via RNA Pol II. In support of this model, Pol II transcription has been shown to occur at human centromeres (Quenet and Dalal 2014;McNulty and Sullivan 2017) and to be functionally important in budding yeast centromeres (Ohkuni and Kitagawa 2011). Pol I has similarly been suggested to be involved in human centromere function (Wong, et al 2007).…”

Section: Discussionmentioning

confidence: 90%

Non-B-form DNA structures mark centromeres

Kasinathan

Henikoff

2017

Preprint

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Animal and plant centromeres are embedded in repetitive "satellite" DNA, but are thought to be epigenetically specified. To define genetic characteristics of centromeres, we surveyed satellite DNA from diverse eukaryotes and identified variation in <10-bp dyad symmetries predicted to adopt non-Bform conformations. Organisms lacking centromeric dyad symmetries had binding sites for sequencespecific DNA binding proteins with DNA bending activity. For example, human and mouse centromeres are depleted for dyad symmetries, but are enriched for non-B DNA and are associated with binding sites for the conserved DNA-binding protein CENP-B, which is required for artificial centromere function but is paradoxically non-essential. We also detected dyad symmetries and predicted non-B-form DNA structures at neocentromeres, which form at ectopic loci. We propose that centromeres form at non-Bform DNA because of dyad symmetries or are strengthened by sequence-specific DNA binding proteins.Our findings resolve the CENP-B paradox and provide a general basis for centromere specification.

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“…Knock-downs of alpha-satellite transcripts (McNulty and Sullivan, 2017) and of a LINE-1 element associated with a neocentromere (Chueh et al, 2009) lead to a decrease in the levels of CENP-A from the (neo)centromeres these transcripts originate from, suggesting they play a localized role in centromere maintenance or stability. In contrast, in S. pombe, centromere-derived transcripts are rapidly degraded by the exosome and are thus unlikely to play such a structural role, but rather appear to be byproducts of centromere transcription (Choi et al, 2011).…”

Section: Resultsmentioning

confidence: 99%

Transcription of a centromere-enriched retroelement and local retention of its RNA are significant features of the CENP-A chromatin landscape

Santinello,

Sun,

Amjad

et al. 2024

Preprint

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Centromeres are essential chromosomal landmarks that dictate the point of attachment between chromosomes and spindle microtubules during cell division. The stable transmission of the centromere site through generations is ensured by a unique chromatin containing the histone H3 variant CENP-A. Previous studies have highlighted the impact of transcription on promoting CENP-A deposition. However, the specific sequences undergoing this transcription and their contribution to centromere function in metazoan systems remain elusive. In this study, we unveil the centromeric transcriptional landscape and explore its correlation with CENP-A in D. melanogaster, currently the only in vivo model with assembled centromeres. We find that the centromere-enriched retroelement G2/Jockey-3 (hereafter referred to as Jockey-3) is a major driver of centromere transcription, producing RNAs that localize to all mitotic centromeres, with the Y centromere showing the most transcription. Taking advantage of the polymorphism of Jockey-3, we show that these RNAs remain associated with their cognate DNA sequences in cis. Using a LacI/lacO system to generate de novo centromeres, we find that Jockey-3 transcripts do not localize to ectopic sites, suggesting they are unlikely to function as non-coding RNAs with a structural role at centromeres. At de novo centromeres on the lacO array, the presence of CENP-A similarly augments the detection of exogenous lacO-derived transcripts specifically in metaphase. We propose that Jockey-3 contributes to the epigenetic maintenance of the centromere by promoting chromatin transcription, while inserting in a region that permits its continuous transmission. Given the conservation of retroelements as centromere components across taxa, our findings have broad implications in understanding this widespread association.

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Centromere Silencing Mechanisms

Cited by 9 publications

References 106 publications

Non-B-Form DNA Is Enriched at Centromeres

Non-B-Form DNA Is Enriched at Centromeres

Non-B-form DNA structures mark centromeres

Transcription of a centromere-enriched retroelement and local retention of its RNA are significant features of the CENP-A chromatin landscape

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