CENP-B creates alternative epigenetic chromatin states permissive for CENP-A or heterochromatin assembly

Otake, Kazuo; Ohzeki, Jun-ichirou; Shono, Nobuaki; Kugou, Kazuto; Okazaki, Keishi; Nagase, Takahiro; Yamakawa, Hisashi; Kouprina, Natalay; Larionov, Vladimir; Kimurâ, Hiroshi; Earnshaw, William C.; Masumoto, Hiroshi

doi:10.1242/jcs.243303

Cited by 37 publications

(71 citation statements)

References 79 publications

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“…Possibly, the chromatin environment or posttranslational modifications might also regulate CENP-C recruitment. Concerning this aspect, the acidic domain of CENP-B was recently described to function as an interface for several chromatin remodeling proteins with either chromatin compaction or decompaction activities (Otake et al, 2020). Although the precise regulation of these CENP-B-mediated chromatin alterations remains unclear, chromatin compaction could impair CENP-C recruitment and thus explain partial CENP-C recruitment.…”

Section: Discussionmentioning

confidence: 99%

A genetic memory initiates the epigenetic loop necessary to preserve centromere position

et al. 2020

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Centromeres are built on repetitive DNA sequences (CenDNA) and a specific chromatin enriched with the histone H3 variant CENP-A, the epigenetic mark that identifies centromere position. Here, we interrogate the importance of CenDNA in centromere specification by developing a system to rapidly remove and reactivate CENP-A (CENP-A OFF/ ON). Using this system, we define the temporal cascade of events necessary to maintain centromere position. We unveil that CENP-B bound to CenDNA provides memory for maintenance on human centromeres by promoting de novo CENP-A deposition. Indeed, lack of CENP-B favors neocentromere formation under selective pressure. Occasionally, CENP-B triggers centromere re-activation initiated by CENP-C, but not CENP-A, recruitment at both ectopic and native centromeres. This is then sufficient to initiate the CENP-A-based epigenetic loop. Finally, we identify a population of CENP-A-negative, CENP-B/C-positive resting CD4 + T cells capable to re-express and reassembles CENP-A upon cell cycle entry, demonstrating the physiological importance of the genetic memory.

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Section: Discussionmentioning

confidence: 99%

A genetic memory initiates the epigenetic loop necessary to preserve centromere position

et al. 2020

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“…Interestingly, a recent study showed that CENP-B serves as a “beacon” for H3.3 incorporation [ 129 ]. Furthermore, in a recent fluorescence microscopy-based interaction-trap assay, components of both heterochromatin (SUV39H1 and HP1) and open chromatin (including histone methyltransferases ASH1L and NSD1) were recruited by CENP-B [ 130 ]. These results point towards a role for CENP-B in organizing centromeric chromatin structures to be competent for both new CENP-A loading and heterochromatin formation.…”

Section: Functions Of Centromeric Transcriptionmentioning

confidence: 99%

Centromeric Transcription: A Conserved Swiss-Army Knife

Arunkumar

Melters

2020

Genes

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In most species, the centromere is comprised of repetitive DNA sequences, which rapidly evolve. Paradoxically, centromeres fulfill an essential function during mitosis, as they are the chromosomal sites wherein, through the kinetochore, the mitotic spindles bind. It is now generally accepted that centromeres are transcribed, and that such transcription is associated with a broad range of functions. More than a decade of work on this topic has shown that centromeric transcripts are found across the eukaryotic tree and associate with heterochromatin formation, chromatin structure, kinetochore structure, centromeric protein loading, and inner centromere signaling. In this review, we discuss the conservation of small and long non-coding centromeric RNAs, their associations with various centromeric functions, and their potential roles in disease.

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“…Previous results have revealed that CENP-B can have a dual role in recruiting centrochromatin or heterochromatin markers depending on the context. 10 , 27 , 41 We speculate that the alphoid 2domain HAC shows 3 types of chromatin. Some of the CENP-B-rich arrays form classical centrochromatin 42 containing CENP-A, H3K4me2 and H3K36me2, but others form H3K9me3-rich heterochromatin, which previous studies have shown to be incompatible with centrochromatin.…”

Section: Discussionmentioning

confidence: 77%

Analysis of Complex DNA Rearrangements during Early Stages of HAC Formation

et al. 2020

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Human artificial chromosomes (HACs) are important tools for epigenetic engineering, for measuring chromosome instability (CIN), and for possible gene therapy. However, their use in the latter is potentially limited because the input HAC-seeding DNA can undergo an unpredictable series of rearrangements during HAC formation. As a result, after transfection and HAC formation, each cell clone contains a HAC with a unique structure that cannot be precisely predicted from the structure of the HAC-seeding DNA. Although it has been reported that these rearrangements can happen, the timing and mechanism of their formation has yet to be described. Here we synthesized a HAC-seeding DNA with two distinct structural domains and introduced it into HT1080 cells. We characterized a number of HAC-containing clones and subclones to track DNA rearrangements during HAC establishment. We demonstrated that rearrangements can occur early during HAC formation. Subsequently, the established HAC genomic organization is stably maintained across many cell generations. Thus, early stages in HAC formation appear to at least occasionally involve a process of DNA shredding and shuffling that resembles chromothripsis, an important hallmark of many cancer types. Understanding these events during HAC formation has critical implications for future efforts aimed at synthesizing and exploiting synthetic human chromosomes.

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CENP-B creates alternative epigenetic chromatin states permissive for CENP-A or heterochromatin assembly

Cited by 37 publications

References 79 publications

A genetic memory initiates the epigenetic loop necessary to preserve centromere position

A genetic memory initiates the epigenetic loop necessary to preserve centromere position

Centromeric Transcription: A Conserved Swiss-Army Knife

Analysis of Complex DNA Rearrangements during Early Stages of HAC Formation

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