Telomere Repeat-Binding Factor 2 Is Responsible for the Telomere Attachment to the Nuclear Membrane

Ilicheva, Nadya V; Podgornaya, O. I.; Voronin, A.P.

doi:10.1016/bs.apcsb.2015.06.009

Cited by 14 publications

(8 citation statements)

References 102 publications

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“…ABs against TRF2 do not have cross-reactivity with TRF1. The band correspond to the apparent molecular mass (Mr) of 70 kDa while TRF1 Mr is 60 kDa [ 43 , 59 ]. ABs against Lamin A and Lamin B also do not react with the opposite type.…”

Section: Resultsmentioning

confidence: 99%

Nucleolus-like body of mouse oocytes contains lamin A and B and TRF2 but not actin and topo II

2016

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BackgroundDuring the final stages of oocyte development, all chromosomes join in a limited nuclear volume for the final formation of a single complex chromatin structure – the karyosphere. In the majority of mammalian species, the chromosomes surround a round protein/fibrillar body known as the central body, or nucleolus-like body (NLB). Nothing seems to unite the inner portion of the karyosphere with the nucleolus except position at its remnants. Nevertheless, in this study we will use term NLB as the conventional one for karyosphere with the central body. At the morphological level, NLBs consist of tightly-packed fibres of 6–10 nm. The biochemical structure of this dense, compact NLB fibre centre remains uncertain.ResultsThe aim of this study was to determine which proteins represent the NLB components at final stages of karyosphere formation in mouse oogenesis. To determine this, three antibodies (ABs) have been examined against different actin epitopes. Examination of both ABs against the actin N-end provided similar results: spots inside the nucleus. Double staining with AB against SC35 and actin revealed the colocalization of these proteins in IGCs (interchromatin granule clusters/nuclear speckles/SC35 domains). In contrast, examination of polyclonal AB against peptide at the C-end reveals a different result: actin is localized exclusively in connection with the chromatin. Surprisingly, no forms of actin or topoisomerase II are present as components of the NLB. It was discovered that: (1) lamin B is an NLB component from the beginning of NLB formation, and a major portion of it resides in the NLB at the end of oocyte development; (2) lamin A undergoes rapid movement into the NLB, and a majority of it remains in the NLB; (3) the telomere-binding protein TRF2 resides in the IGCs/nuclear speckles until the end of oocyte development, when significant part of it transfers to the NLB.ConclusionsNLBs do not contain actin or topo II. Lamin B is involved from the beginning of NLB formation. Both Lamin A and TRF2 exhibit rapid movement to the NLB at the end of oogenesis. This dynamic distribution of proteins may reflect the NLB’s role in future chromatin organization post-fertilisation.

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Section: Resultsmentioning

confidence: 99%

Nucleolus-like body of mouse oocytes contains lamin A and B and TRF2 but not actin and topo II

2016

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“…Telomeric DNA of most eukaryotes is composed of short tandemly repeated sequences T 2 AG 3 for all vertebrates and thus it represents a TR class [ 31 , 50 ] . Telomeric repeat is absent in Repbase, so the search for it was accomplished by mapping of ChrmC dataset to (T 2 AG 3 ) 20 .…”

Section: Resultsmentioning

confidence: 99%

Mouse chromocenters DNA content: sequencing and in silico analysis

et al. 2018

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BackgroundChromocenters are defined as a punctate condensed blocks of chromatin in the interphase cell nuclei of certain cell types with unknown biological significance. In recent years a progress in revealing of chromocenters protein content has been made although the details of DNA content within constitutive heterochromatin still remain unclear. It is known that these regions are enriched in tandem repeats (TR) and transposable elements. Quick improvement of genome sequencing does not help to assemble the heterochromatic regions due to lack of appropriate bioinformatics techniques.ResultsChromocenters DNA have been isolated by a biochemical approach from mouse liver cells nuclei and sequenced on the Illumina MiSeq resulting in ChrmC dataset. Analysis of ChrmC dataset by the bioinformatics tools available revealed that the major component of chromocenter DNA are TRs: ~ 66% MaSat and ~ 4% MiSat. Other previously classified TR families constitute ~ 1% of ChrmC dataset. About 6% of chromocenters DNA are mostly unannotated sequences. In the contigs assembled with IDBA_UD there are many fragments of heterochromatic Y-chromosome, rDNA and other pseudo-genes and non-coding DNA. A protein coding sfi1 homolog gene fragment was also found in contigs. The Sfi1 homolog gene is located on the chromosome 11 in the reference genome very close to the Golden Pass Gap (a ~ 3 Mb empty region reserved to the pericentromeric region) and proves the purity of chromocenters isolation. The second major fraction are non-LTR retroposons (SINE and LINE) with overwhelming majority of LINE - ~ 11% of ChrmC. Most of the LINE fragments are from the ~ 2 kb region at the end of the 2nd ORF and its’ flanking region. The precise LINEs’ segment of ~ 2 kb is the necessary mouse constitutive heterohromatin component together with TR. The third most abundant fraction are ERVs. The ERV distribution in chromocenters differs from the whole genome: IAP (ERV2 class) is the most numerous in ChrmC while MaLR (ERV3 class) prevails in the reference genome. IAP and its LTR also prevail in TR containing contigs extracted from the WGS dataset. In silico prediction of IAP and LINE fragments in chromocenters was confirmed by direct fluorescent in situ hybridization (FISH).ConclusionOur data of chromocenters’ DNA (ChrmC) sequencing demonstrate that IAP with LTR and a precise ~ 2 kb fragment of LINE represent a substantial fraction of mouse chromocenters (constitutive heteroсhromatin) along with TRs.Electronic supplementary materialThe online version of this article (10.1186/s12864-018-4534-z) contains supplementary material, which is available to authorized users.

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“…We showed that the association between lamin B1 and TRF2 implicates the head-coil 1 domain of lamin B1 and the flexible hinge region (or linker) of TRF2, a region implicated in protein-protein interactions, including binding with RAP1 ( 4 , 8 , 76 ) and that both shelterin proteins are required to form stable complexes with lamin B1. It has been reported that the linker of TRF2 presents structural similarities with rod domains of intermediate filaments ( 77 ) and is involved in DNA-specific oligomerization of TRF2 ( 78 ). Likewise, the head-coil1 domain of lamin B1, contains coiled-coil motifs also involved in lamin oligomerization.…”

Section: Discussionmentioning

confidence: 99%

Increase in lamin B1 promotes telomere instability by disrupting the shelterin complex in human cells

Pennarun

Picotto

Etourneaud

et al. 2021

Nucleic Acids Research

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Telomere maintenance is essential to preserve genomic stability and involves telomere-specific proteins, DNA replication and repair proteins. Lamins are key components of the nuclear envelope and play numerous roles, including maintenance of the nuclear integrity, regulation of transcription, and DNA replication. Elevated levels of lamin B1, one of the major lamins, have been observed in some human pathologies and several cancers. Yet, the effect of lamin B1 dysregulation on telomere maintenance remains unknown. Here, we unveil that lamin B1 overexpression drives telomere instability through the disruption of the shelterin complex. Indeed, lamin B1 dysregulation leads to an increase in telomere dysfunction-induced foci, telomeric fusions and telomere losses in human cells. Telomere aberrations were preceded by mislocalizations of TRF2 and its binding partner RAP1. Interestingly, we identified new interactions between lamin B1 and these shelterin proteins, which are strongly enhanced at the nuclear periphery upon lamin B1 overexpression. Importantly, chromosomal fusions induced by lamin B1 in excess were rescued by TRF2 overexpression. These data indicated that lamin B1 overexpression triggers telomere instability through a mislocalization of TRF2. Altogether our results point to lamin B1 as a new interacting partner of TRF2, that is involved in telomere stability.

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Telomere Repeat-Binding Factor 2 Is Responsible for the Telomere Attachment to the Nuclear Membrane

Cited by 14 publications

References 102 publications

Nucleolus-like body of mouse oocytes contains lamin A and B and TRF2 but not actin and topo II

Nucleolus-like body of mouse oocytes contains lamin A and B and TRF2 but not actin and topo II

Mouse chromocenters DNA content: sequencing and in silico analysis

Increase in lamin B1 promotes telomere instability by disrupting the shelterin complex in human cells

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