The chromatin remodeling protein CHD-1 and the EFL-1/DPL-1 transcription factor cooperatively down regulate CDK-2 to control SAS-6 levels and centriole number.

Autor: Iyer J; Department of Chemistry and Biochemistry, University of Tulsa, Tulsa, Oklahoma, United States of America., Gentry LK; Laboratory of Biochemistry and Genetics, National Institutes of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, United States of America., Bergwell M; Department of Chemistry and Biochemistry, University of Tulsa, Tulsa, Oklahoma, United States of America., Smith A; Department of Chemistry and Biochemistry, University of Tulsa, Tulsa, Oklahoma, United States of America., Guagliardo S; Laboratory of Biochemistry and Genetics, National Institutes of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, United States of America., Kropp PA; Laboratory of Biochemistry and Genetics, National Institutes of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, United States of America., Sankaralingam P; Laboratory of Biochemistry and Genetics, National Institutes of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, United States of America., Liu Y; Laboratory of Biochemistry and Genetics, National Institutes of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, United States of America., Spooner E; Proteomics Core Facility, Whitehead Institute for Biomedical Research, Cambridge Massachusetts, United States of America., Bowerman B; Institute of Molecular Biology, University of Oregon, Eugene, Oregon, United States of America., O'Connell KF; Laboratory of Biochemistry and Genetics, National Institutes of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, United States of America.
Jazyk: angličtina
Zdroj: PLoS genetics [PLoS Genet] 2022 Apr 04; Vol. 18 (4), pp. e1009799. Date of Electronic Publication: 2022 Apr 04 (Print Publication: 2022).
DOI: 10.1371/journal.pgen.1009799
Abstrakt: Centrioles are submicron-scale, barrel-shaped organelles typically found in pairs, and play important roles in ciliogenesis and bipolar spindle assembly. In general, successful execution of centriole-dependent processes is highly reliant on the ability of the cell to stringently control centriole number. This in turn is mainly achieved through the precise duplication of centrioles during each S phase. Aberrations in centriole duplication disrupt spindle assembly and cilia-based signaling and have been linked to cancer, primary microcephaly and a variety of growth disorders. Studies aimed at understanding how centriole duplication is controlled have mainly focused on the post-translational regulation of two key components of this pathway: the master regulatory kinase ZYG-1/Plk4 and the scaffold component SAS-6. In contrast, how transcriptional control mechanisms might contribute to this process have not been well explored. Here we show that the chromatin remodeling protein CHD-1 contributes to the regulation of centriole duplication in the C. elegans embryo. Specifically, we find that loss of CHD-1 or inactivation of its ATPase activity can restore embryonic viability and centriole duplication to a strain expressing insufficient ZYG-1 activity. Interestingly, loss of CHD-1 is associated with increases in the levels of two ZYG-1-binding partners: SPD-2, the centriole receptor for ZYG-1 and SAS-6. Finally, we explore transcriptional regulatory networks governing centriole duplication and find that CHD-1 and a second transcription factor, EFL-1/DPL-1 cooperate to down regulate expression of CDK-2, which in turn promotes SAS-6 protein levels. Disruption of this regulatory network results in the overexpression of SAS-6 and the production of extra centrioles.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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