The adenomatous polyposis coli protein contributes to normal compaction of mitotic chromatin.
The tumour suppressor Adenomatous Polyposis Coli (APC) is required for proper mitosis; however, the exact role of APC in mitosis is not understood. Using demembranated sperm chromatin exposed to meiotic Xenopus egg extract and HeLa cells expressing fluorescently labelled histones, we established tha...
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2012-01-01
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doaj-830b131551ad4be4a691057c3a0f2f192020-11-25T01:53:42ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0176e3810210.1371/journal.pone.0038102The adenomatous polyposis coli protein contributes to normal compaction of mitotic chromatin.Dina DikovskayaGuennadi KhoudoliIan P NewtonGaganmeet S ChadhaDaniel KlotzAshwat VisvanathanAngus LamondJason R SwedlowInke S NäthkeThe tumour suppressor Adenomatous Polyposis Coli (APC) is required for proper mitosis; however, the exact role of APC in mitosis is not understood. Using demembranated sperm chromatin exposed to meiotic Xenopus egg extract and HeLa cells expressing fluorescently labelled histones, we established that APC contributes to chromatin compaction. Sperm chromatin in APC-depleted Xenopus egg extract frequently formed tight round or elongated structures. Such abnormally compacted chromatin predominantly formed spindles with low microtubule content. Furthermore, in mitotic HeLa cells expressing GFP- and mCherry-labelled H2B histones, depletion of APC caused a decrease in the donor fluorescence lifetime of neighbouring fluorophores, indicative of excessive chromatin compaction. Profiling the chromatin-associated proteome of sperm chromatin incubated with Xenopus egg extracts revealed temporal APC-dependent changes in the abundance of histones, closely mirrored by chromatin-associated Topoisomerase IIa, condensin I complex and Kif4. In the absence of APC these factors initially accumulated on chromatin, but then decreased faster than in controls. We also found and validated significant APC-dependent changes in chromatin modifiers Set-a and Rbbp7. Both were decreased on chromatin in APC-depleted extract; in addition, the kinetics of association of Set-a with chromatin was altered in the absence of APC.http://europepmc.org/articles/PMC3374815?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Dina Dikovskaya Guennadi Khoudoli Ian P Newton Gaganmeet S Chadha Daniel Klotz Ashwat Visvanathan Angus Lamond Jason R Swedlow Inke S Näthke |
spellingShingle |
Dina Dikovskaya Guennadi Khoudoli Ian P Newton Gaganmeet S Chadha Daniel Klotz Ashwat Visvanathan Angus Lamond Jason R Swedlow Inke S Näthke The adenomatous polyposis coli protein contributes to normal compaction of mitotic chromatin. PLoS ONE |
author_facet |
Dina Dikovskaya Guennadi Khoudoli Ian P Newton Gaganmeet S Chadha Daniel Klotz Ashwat Visvanathan Angus Lamond Jason R Swedlow Inke S Näthke |
author_sort |
Dina Dikovskaya |
title |
The adenomatous polyposis coli protein contributes to normal compaction of mitotic chromatin. |
title_short |
The adenomatous polyposis coli protein contributes to normal compaction of mitotic chromatin. |
title_full |
The adenomatous polyposis coli protein contributes to normal compaction of mitotic chromatin. |
title_fullStr |
The adenomatous polyposis coli protein contributes to normal compaction of mitotic chromatin. |
title_full_unstemmed |
The adenomatous polyposis coli protein contributes to normal compaction of mitotic chromatin. |
title_sort |
adenomatous polyposis coli protein contributes to normal compaction of mitotic chromatin. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2012-01-01 |
description |
The tumour suppressor Adenomatous Polyposis Coli (APC) is required for proper mitosis; however, the exact role of APC in mitosis is not understood. Using demembranated sperm chromatin exposed to meiotic Xenopus egg extract and HeLa cells expressing fluorescently labelled histones, we established that APC contributes to chromatin compaction. Sperm chromatin in APC-depleted Xenopus egg extract frequently formed tight round or elongated structures. Such abnormally compacted chromatin predominantly formed spindles with low microtubule content. Furthermore, in mitotic HeLa cells expressing GFP- and mCherry-labelled H2B histones, depletion of APC caused a decrease in the donor fluorescence lifetime of neighbouring fluorophores, indicative of excessive chromatin compaction. Profiling the chromatin-associated proteome of sperm chromatin incubated with Xenopus egg extracts revealed temporal APC-dependent changes in the abundance of histones, closely mirrored by chromatin-associated Topoisomerase IIa, condensin I complex and Kif4. In the absence of APC these factors initially accumulated on chromatin, but then decreased faster than in controls. We also found and validated significant APC-dependent changes in chromatin modifiers Set-a and Rbbp7. Both were decreased on chromatin in APC-depleted extract; in addition, the kinetics of association of Set-a with chromatin was altered in the absence of APC. |
url |
http://europepmc.org/articles/PMC3374815?pdf=render |
work_keys_str_mv |
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