TRF1 Depletion Reveals Mutual Regulation Between Telomeres, Kinetochores, and Inner Centromeres in Mouse Oocytes

In eukaryotic chromosomes, the centromere and telomere are two specialized structures that are essential for chromosome stability and segregation. Although centromeres and telomeres often are located in close proximity to form telocentric chromosomes in mice, it remained unclear whether these two st...

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Main Authors: Hyuk-Joon Jeon, Jeong Su Oh
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-09-01
Series:Frontiers in Cell and Developmental Biology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2021.749116/full
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author Hyuk-Joon Jeon
Jeong Su Oh
author_facet Hyuk-Joon Jeon
Jeong Su Oh
author_sort Hyuk-Joon Jeon
collection DOAJ
description In eukaryotic chromosomes, the centromere and telomere are two specialized structures that are essential for chromosome stability and segregation. Although centromeres and telomeres often are located in close proximity to form telocentric chromosomes in mice, it remained unclear whether these two structures influence each other. Here we show that TRF1 is required for inner centromere and kinetochore assembly in addition to its role in telomere protection in mouse oocytes. TRF1 depletion caused premature chromosome segregation by abrogating the spindle assembly checkpoint (SAC) and impairing kinetochore-microtubule (kMT) attachment, which increased the incidence of aneuploidy. Notably, TRF1 depletion disturbed the localization of Survivin and Ndc80/Hec1 at inner centromeres and kinetochores, respectively. Moreover, SMC3 and SMC4 levels significantly decreased after TRF1 depletion, suggesting that TRF1 is involved in chromosome cohesion and condensation. Importantly, inhibition of inner centromere or kinetochore function led to a significant decrease in TRF1 level and telomere shortening. Therefore, our results suggest that telomere integrity is required to preserve inner centromere and kinetochore architectures, and vice versa, suggesting mutual regulation between telomeres and centromeres.
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spelling doaj.art-4678fa6bdd104a0dbfdd6494312612152022-12-21T23:32:44ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-09-01910.3389/fcell.2021.749116749116TRF1 Depletion Reveals Mutual Regulation Between Telomeres, Kinetochores, and Inner Centromeres in Mouse OocytesHyuk-Joon JeonJeong Su OhIn eukaryotic chromosomes, the centromere and telomere are two specialized structures that are essential for chromosome stability and segregation. Although centromeres and telomeres often are located in close proximity to form telocentric chromosomes in mice, it remained unclear whether these two structures influence each other. Here we show that TRF1 is required for inner centromere and kinetochore assembly in addition to its role in telomere protection in mouse oocytes. TRF1 depletion caused premature chromosome segregation by abrogating the spindle assembly checkpoint (SAC) and impairing kinetochore-microtubule (kMT) attachment, which increased the incidence of aneuploidy. Notably, TRF1 depletion disturbed the localization of Survivin and Ndc80/Hec1 at inner centromeres and kinetochores, respectively. Moreover, SMC3 and SMC4 levels significantly decreased after TRF1 depletion, suggesting that TRF1 is involved in chromosome cohesion and condensation. Importantly, inhibition of inner centromere or kinetochore function led to a significant decrease in TRF1 level and telomere shortening. Therefore, our results suggest that telomere integrity is required to preserve inner centromere and kinetochore architectures, and vice versa, suggesting mutual regulation between telomeres and centromeres.https://www.frontiersin.org/articles/10.3389/fcell.2021.749116/fulltelomerecentromerekinetochoreTRF1oocyte
spellingShingle Hyuk-Joon Jeon
Jeong Su Oh
TRF1 Depletion Reveals Mutual Regulation Between Telomeres, Kinetochores, and Inner Centromeres in Mouse Oocytes
Frontiers in Cell and Developmental Biology
telomere
centromere
kinetochore
TRF1
oocyte
title TRF1 Depletion Reveals Mutual Regulation Between Telomeres, Kinetochores, and Inner Centromeres in Mouse Oocytes
title_full TRF1 Depletion Reveals Mutual Regulation Between Telomeres, Kinetochores, and Inner Centromeres in Mouse Oocytes
title_fullStr TRF1 Depletion Reveals Mutual Regulation Between Telomeres, Kinetochores, and Inner Centromeres in Mouse Oocytes
title_full_unstemmed TRF1 Depletion Reveals Mutual Regulation Between Telomeres, Kinetochores, and Inner Centromeres in Mouse Oocytes
title_short TRF1 Depletion Reveals Mutual Regulation Between Telomeres, Kinetochores, and Inner Centromeres in Mouse Oocytes
title_sort trf1 depletion reveals mutual regulation between telomeres kinetochores and inner centromeres in mouse oocytes
topic telomere
centromere
kinetochore
TRF1
oocyte
url https://www.frontiersin.org/articles/10.3389/fcell.2021.749116/full
work_keys_str_mv AT hyukjoonjeon trf1depletionrevealsmutualregulationbetweentelomereskinetochoresandinnercentromeresinmouseoocytes
AT jeongsuoh trf1depletionrevealsmutualregulationbetweentelomereskinetochoresandinnercentromeresinmouseoocytes