Drosophila casein kinase I alpha regulates homolog pairing and genome organization by modulating condensin II subunit Cap-H2 levels.
The spatial organization of chromosomes within interphase nuclei is important for gene expression and epigenetic inheritance. Although the 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.
Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America.
Huy Q
HQ
Nguyen
Department of Cellular and Molecular Medicine, University of Arizona Cancer Center, University of Arizona, Tucson, Arizona, United States of America.
Jonathan
J
Nye
Department of Cellular and Molecular Medicine, University of Arizona Cancer Center, University of Arizona, Tucson, Arizona, United States of America.
Daniel W
DW
Buster
Department of Cellular and Molecular Medicine, University of Arizona Cancer Center, University of Arizona, Tucson, Arizona, United States of America.
Joseph E
JE
Klebba
Department of Cellular and Molecular Medicine, University of Arizona Cancer Center, University of Arizona, Tucson, Arizona, United States of America.
Gregory C
GC
Rogers
Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America.
Giovanni
G
Bosco
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D048128:Casein Kinase Ialpha / Q000235:genetics* / Q000378:metabolism; D002503:Centromere / Q000235:genetics; D002843:Chromatin / Q000235:genetics; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000378:metabolism; D023902:Chromosome Pairing / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D008938:Mitosis / Q000235:genetics*; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D012469:Salivary Glands / Q000378:metabolism
C577064:Cap-H2 protein, Drosophila; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D046912:Multiprotein Complexes; C108312:condensin complexes; D048128:Casein Kinase Ialpha; D000251:Adenosine Triphosphatases