Drosophila Casein Kinase I Alpha Regulates Homolog Pairing and Genome Organization by Modulating Condensin II Subunit Cap-H2 Levels

Huy Q. Nguyen, Jonathan Nye, Daniel W. Buster, Joseph E. Klebba, Gregory C. Rogers, Giovanni Bosco

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

The spatial organization of chromosomes within interphase nucleiis important for gene expression and epigenetic inheritance. Althoughthe extent of physical interaction between chromosomes and their degree of compaction varies during development and between different cell-types, it is unclear how regulation of chromosome interactions and compaction relate to spatial organization of genomes. Drosophila is an excellent model system for studying chromosomal interactions including homolog pairing. Recent work has shown that condensin II governs both interphase chromosome compaction and homolog pairing and condensin II activity is controlled by the turnover of its regulatory subunit Cap-H2. Specifically, Cap-H2 is a target of the SCFSlimb E3 ubiquitin-ligase which down-regulates Cap-H2 in order to maintain homologous chromosome pairing, chromosome length and proper nuclear organization. Here, we identify Casein Kinase I alpha (CK1α) as an additional negative-regulator of Cap-H2. CK1α-depletion stabilizes Cap-H2 protein and results in an accumulation of Cap-H2 on chromosomes. Similar to Slimb mutation, CK1α depletion in cultured cells, larval salivary gland, and nurse cells results in several condensin II-dependent phenotypes including dispersal of centromeres, interphase chromosome compaction, and chromosome unpairing. Moreover, CK1α loss-of-function mutations dominantly suppress condensin II mutant phenotypes in vivo. Thus, CK1α facilitates Cap-H2 destruction and modulates nuclear organization by attenuating chromatin localized Cap-H2 protein.

Original languageEnglish (US)
Article numbere1005014
JournalPLoS Genetics
Volume11
Issue number2
DOIs
StatePublished - Feb 27 2015

Fingerprint

Casein Kinase Ialpha
Drosophila
chromosome
genome
Chromosomes
Genome
chromosomes
Interphase
compaction
interphase
phenotype
mutation
Chromosome Pairing
Phenotype
Mutation
ubiquitin-protein ligase
chromosome pairing
Ubiquitin-Protein Ligases
condensin complexes
non-specific serine/threonine protein kinase

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Cancer Research
  • Genetics(clinical)

Cite this

Drosophila Casein Kinase I Alpha Regulates Homolog Pairing and Genome Organization by Modulating Condensin II Subunit Cap-H2 Levels. / Nguyen, Huy Q.; Nye, Jonathan; Buster, Daniel W.; Klebba, Joseph E.; Rogers, Gregory C.; Bosco, Giovanni.

In: PLoS Genetics, Vol. 11, No. 2, e1005014, 27.02.2015.

Research output: Contribution to journalArticle

Nguyen, Huy Q. ; Nye, Jonathan ; Buster, Daniel W. ; Klebba, Joseph E. ; Rogers, Gregory C. ; Bosco, Giovanni. / Drosophila Casein Kinase I Alpha Regulates Homolog Pairing and Genome Organization by Modulating Condensin II Subunit Cap-H2 Levels. In: PLoS Genetics. 2015 ; Vol. 11, No. 2.
@article{323bd4b69dc54306a7062d5846b457fc,
title = "Drosophila Casein Kinase I Alpha Regulates Homolog Pairing and Genome Organization by Modulating Condensin II Subunit Cap-H2 Levels",
abstract = "The spatial organization of chromosomes within interphase nucleiis important for gene expression and epigenetic inheritance. Althoughthe extent of physical interaction between chromosomes and their degree of compaction varies during development and between different cell-types, it is unclear how regulation of chromosome interactions and compaction relate to spatial organization of genomes. Drosophila is an excellent model system for studying chromosomal interactions including homolog pairing. Recent work has shown that condensin II governs both interphase chromosome compaction and homolog pairing and condensin II activity is controlled by the turnover of its regulatory subunit Cap-H2. Specifically, Cap-H2 is a target of the SCFSlimb E3 ubiquitin-ligase which down-regulates Cap-H2 in order to maintain homologous chromosome pairing, chromosome length and proper nuclear organization. Here, we identify Casein Kinase I alpha (CK1α) as an additional negative-regulator of Cap-H2. CK1α-depletion stabilizes Cap-H2 protein and results in an accumulation of Cap-H2 on chromosomes. Similar to Slimb mutation, CK1α depletion in cultured cells, larval salivary gland, and nurse cells results in several condensin II-dependent phenotypes including dispersal of centromeres, interphase chromosome compaction, and chromosome unpairing. Moreover, CK1α loss-of-function mutations dominantly suppress condensin II mutant phenotypes in vivo. Thus, CK1α facilitates Cap-H2 destruction and modulates nuclear organization by attenuating chromatin localized Cap-H2 protein.",
author = "Nguyen, {Huy Q.} and Jonathan Nye and Buster, {Daniel W.} and Klebba, {Joseph E.} and Rogers, {Gregory C.} and Giovanni Bosco",
year = "2015",
month = "2",
day = "27",
doi = "10.1371/journal.pgen.1005014",
language = "English (US)",
volume = "11",
journal = "PLoS Genetics",
issn = "1553-7390",
publisher = "Public Library of Science",
number = "2",

}

TY - JOUR

T1 - Drosophila Casein Kinase I Alpha Regulates Homolog Pairing and Genome Organization by Modulating Condensin II Subunit Cap-H2 Levels

AU - Nguyen, Huy Q.

AU - Nye, Jonathan

AU - Buster, Daniel W.

AU - Klebba, Joseph E.

AU - Rogers, Gregory C.

AU - Bosco, Giovanni

PY - 2015/2/27

Y1 - 2015/2/27

N2 - The spatial organization of chromosomes within interphase nucleiis important for gene expression and epigenetic inheritance. Althoughthe extent of physical interaction between chromosomes and their degree of compaction varies during development and between different cell-types, it is unclear how regulation of chromosome interactions and compaction relate to spatial organization of genomes. Drosophila is an excellent model system for studying chromosomal interactions including homolog pairing. Recent work has shown that condensin II governs both interphase chromosome compaction and homolog pairing and condensin II activity is controlled by the turnover of its regulatory subunit Cap-H2. Specifically, Cap-H2 is a target of the SCFSlimb E3 ubiquitin-ligase which down-regulates Cap-H2 in order to maintain homologous chromosome pairing, chromosome length and proper nuclear organization. Here, we identify Casein Kinase I alpha (CK1α) as an additional negative-regulator of Cap-H2. CK1α-depletion stabilizes Cap-H2 protein and results in an accumulation of Cap-H2 on chromosomes. Similar to Slimb mutation, CK1α depletion in cultured cells, larval salivary gland, and nurse cells results in several condensin II-dependent phenotypes including dispersal of centromeres, interphase chromosome compaction, and chromosome unpairing. Moreover, CK1α loss-of-function mutations dominantly suppress condensin II mutant phenotypes in vivo. Thus, CK1α facilitates Cap-H2 destruction and modulates nuclear organization by attenuating chromatin localized Cap-H2 protein.

AB - The spatial organization of chromosomes within interphase nucleiis important for gene expression and epigenetic inheritance. Althoughthe extent of physical interaction between chromosomes and their degree of compaction varies during development and between different cell-types, it is unclear how regulation of chromosome interactions and compaction relate to spatial organization of genomes. Drosophila is an excellent model system for studying chromosomal interactions including homolog pairing. Recent work has shown that condensin II governs both interphase chromosome compaction and homolog pairing and condensin II activity is controlled by the turnover of its regulatory subunit Cap-H2. Specifically, Cap-H2 is a target of the SCFSlimb E3 ubiquitin-ligase which down-regulates Cap-H2 in order to maintain homologous chromosome pairing, chromosome length and proper nuclear organization. Here, we identify Casein Kinase I alpha (CK1α) as an additional negative-regulator of Cap-H2. CK1α-depletion stabilizes Cap-H2 protein and results in an accumulation of Cap-H2 on chromosomes. Similar to Slimb mutation, CK1α depletion in cultured cells, larval salivary gland, and nurse cells results in several condensin II-dependent phenotypes including dispersal of centromeres, interphase chromosome compaction, and chromosome unpairing. Moreover, CK1α loss-of-function mutations dominantly suppress condensin II mutant phenotypes in vivo. Thus, CK1α facilitates Cap-H2 destruction and modulates nuclear organization by attenuating chromatin localized Cap-H2 protein.

UR - http://www.scopus.com/inward/record.url?scp=84931569114&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84931569114&partnerID=8YFLogxK

U2 - 10.1371/journal.pgen.1005014

DO - 10.1371/journal.pgen.1005014

M3 - Article

C2 - 25723539

AN - SCOPUS:84931569114

VL - 11

JO - PLoS Genetics

JF - PLoS Genetics

SN - 1553-7390

IS - 2

M1 - e1005014

ER -