ORCA/LRWD1 Regulates Homologous Recombination at ALT-Telomeres by Modulating Heterochromatin Organization

Hsu, Rosaline Y.C.; Lin, Yo Chuen; Redon, Christophe E.; Sun, Qinyu; Singh, Deepak Kumar; Wang, Yating; Aggarwal, Vasudha; Mitra, Jaba; Matur, Abhijith V.; Moriarity, Branden S.; Ha, Taekjip; Aladjem, Mirit I.; Prasanth, Kannanganattu V.; Prasanth, Supriya G.

doi:10.1016/j.isci.2020.101038

Cited by 10 publications

(10 citation statements)

References 70 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Accordingly, the expression of the TRF2 ΔB mutant form reduces ORI formation in telomeres by disrupting ORC and the replicative helicase MCM3 [ 21 ]. Other properties of TRF2 could also be involved in its role in pericentromeric replication initiation since it was reported that it associates to ORCA/LRWD1 [ 24 ] and that, in addition to the basic N-terminal domain, the TRF2 dimerization domain is required for ORC recruitment [ 25 ]. An interesting possibility would be that the pericentromeric ORI activity also relies on the ability of TRF2 to bind and unwind the formation of a G-quadruplex structure within the G-rich satellite DNA repeats [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

The Telomeric Protein TRF2 Regulates Replication Origin Activity within Pericentromeric Heterochromatin

Bauwens

Lototska

Koundrioukoff

et al. 2021

Life

View full text Add to dashboard Cite

Heterochromatic regions render the replication process particularly difficult due to the high level of chromatin compaction and the presence of repeated DNA sequences. In humans, replication through pericentromeric heterochromatin requires the binding of a complex formed by the telomeric factor TRF2 and the helicase RTEL1 in order to relieve topological barriers blocking fork progression. Since TRF2 is known to bind the Origin Replication Complex (ORC), we hypothesized that this factor could also play a role at the replication origins (ORI) of these heterochromatin regions. By performing DNA combing analysis, we found that the ORI density is higher within pericentromeric satellite DNA repeats than within bulk genomic DNA and decreased upon TRF2 downregulation. Moreover, we showed that TRF2 and ORC2 interact in pericentromeric DNA, providing a mechanism by which TRF2 is involved in ORI activity. Altogether, our findings reveal an essential role for TRF2 in pericentromeric heterochromatin replication by regulating both replication initiation and elongation.

show abstract

Section: Discussionmentioning

confidence: 99%

The Telomeric Protein TRF2 Regulates Replication Origin Activity within Pericentromeric Heterochromatin

Bauwens

Lototska

Koundrioukoff

et al. 2021

Life

View full text Add to dashboard Cite

show abstract

“…Accordingly, TGFBr1 has been shown to regulate C2C12 myoblast proliferation and differentiation by triggering the Smad3 signaling pathway [ 30 , 31 ]. In addition, TGFBs and TGFBRs are reported to be highly associated with myoblast differentiation (including fusion and myogenesis) and as the regulator of MRFs [ 32 , 33 , 34 ]. It has been reported that FGF7 is up-regulated in differentiated myofibers [ 35 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

The Essential Role of Stathmin in Myoblast C2C12 for Vertical Vibration-Induced Myotube Formation

Lin

Chou

et al. 2021

Biomolecules

View full text Add to dashboard Cite

Vertical vibration (VV) is a type of whole body vibration, which induces muscle contraction through vibration to improve muscle strength and bone density. However, the mechanism of VV on muscle cell myotube formation is still unclear. In the current study, we aim to clarify the mechanism involved in VV’s stimulation of myotube formation. In order to identify the molecules regulated by VV, we performed proteomics analysis including 2D electrophoresis combined with MALDI-TOF/TOF Mass. Stathmin was identified as a high potential molecule responding to VV stimulation, and we found that under VV stimulation, the expression of stathmin gene and protein increased in a time-dependent manner. In addition, we also confirmed that the increase of stathmin stimulated by VV is mediated through the PI3K/Akt pathway. Furthermore, stathmin siRNA significantly down-regulated the expression of myogenic regulatory factor (MRF) MyoD, decorin, and type I collagen (Col-I), and down-regulated the cellular process regulators such as FGF7, TGFBr1 and PAK3. Taken together, our results confirm that under the stimulation of VV, PI3K/Akt and stathmin would be activated, as well as the up-regulation of MRFs, such as FGF7, TGFBr1 and PAK3 to initiate myogenesis. It also showed that the response of MRF to VV stimulation was significantly related to stathmin expression, which also confirmed the importance of stathmin in the entire myotube formation process. This study may provide evidence of stathmin as a biological indicator of VV to increase muscle strength.

show abstract

“…These genes all have their known functions linked to chromatin state. For example, LRWD1 is a subunit of the origin recognition complex (ORC) and plays a role in heterochromatin organization and cell cycle control (20)(21)(22)(23). KAT2A (also known as GCN5), a histone acetyltransferase, and SUV39H1, a histone methyltransferase that trimethylates lysine 9 of histone H3, are most highly studied histone enzymes and play pivotal roles in the epigenetic landscape and chromatin modification (24,25).…”

Section: Translational Switch Occurs During Bovine Major Egamentioning

confidence: 99%

High-resolution Ribosome Profiling Reveals Translational Selectivity for Transcripts in Bovine Preimplantation Embryo Development

Jiang¹,

Zhu²,

Tong

et al. 2022

Preprint

View full text Add to dashboard Cite

High resolution ribosome fractionation and low-input ribosome profiling of bovine oocytes and preimplantation embryos has enabled us to define the translational landscapes of early embryo development at an unprecedented level. We analyzed the transcriptome, polysome- and non-polysome-bound RNA profiles of bovine oocytes (GV and MII stage) and early embryos at 2-, 8-cell, morula, and blastocyst stage, and revealed four modes of translational selectivity: i. selective translation of non-abundant mRNAs, ii. active, but modest translation of a selection of highly expressed mRNAs, iii. translationally suppressed abundant to moderately abundant mRNAs, and iv. mRNAs associated specifically with monosomes. A strong translational selection of low abundance mRNAs encoding protein components involved in metabolic pathways and lysosome was found throughout bovine oocyte and preimplantation development. In particular, genes encoding components involved in mitochondrial function were prioritized for translation. Notably, transcripts encoding proteins regulating chromatin modifications selectively translated in oocytes. We found that the translational dynamics largely reflects transcriptional profiles in oocytes and 2-cell embryos, but observed marked shift in translational control in 8-cell embryos associated with the main phase of embryonic genome activation. Subsequently, transcription and translation become better synchronized in morulae and blastocysts. Together, these data reveal a unique spatiotemporal translational regulation that accompanies bovine preimplantation development.

show abstract

ORCA/LRWD1 Regulates Homologous Recombination at ALT-Telomeres by Modulating Heterochromatin Organization

Cited by 10 publications

References 70 publications

The Telomeric Protein TRF2 Regulates Replication Origin Activity within Pericentromeric Heterochromatin

The Telomeric Protein TRF2 Regulates Replication Origin Activity within Pericentromeric Heterochromatin

The Essential Role of Stathmin in Myoblast C2C12 for Vertical Vibration-Induced Myotube Formation

High-resolution Ribosome Profiling Reveals Translational Selectivity for Transcripts in Bovine Preimplantation Embryo Development

Contact Info

Product

Resources

About