Cell Cycle-Regulated Transcription of CENP-A by the MBF Complex Ensures Optimal Level of CENP-A for Centromere Formation.
In: Genetics, Jg. 211 (2019-03-01), Heft 3, S. 861-875
Online
academicJournal
Zugriff:
The centromere plays an essential role in chromosome segregation. In most eukaryotes, centromeres are epigenetically defined by the conserved histone H3 variant CENP-A. Proper centromere assembly is dependent upon the tight regulation of CENP-A level. Cell cycle regulation of CENP-A transcription appears to be a universal feature across eukaryotes, but the molecular mechanism underlying the temporal control of CENP-A transcription and how such regulation contributes to centromere function remains elusive. CENP-A in fission yeast has been shown to be transcribed before S phase. Using various synchronization methods, we confirmed that CENP-A transcription occurs at G1, leading to an almost twofold increase of the protein during S phase. Through a genetic screen, we identified the MBF (MluI box-binding factors) complex as a key regulator of temporal control of CENP-A transcription. The periodic transcription of CENP-A is lost in MBF mutants, resulting in CENP-A mislocalization and chromosome segregation defects. We identified the MCB (MluI cell cycle box) motif in the CENP-A promoter, and further showed that the MBF complex binds to the motif to restrict CENP-A transcription to G1. Mutations of the MCB motif cause constitutive CENP-A expression and deleterious effects on cell survival. Using promoters driving transcription to different cell cycle stages, we found that timing of CENP-A transcription is dispensable for its centromeric localization. Our data instead indicate that cell cycle-regulated CENP-A transcription is a key step to ensure that a proper amount of CENP-A is generated across generations. This study provides mechanistic insights into the regulation of cell cycledependent CENP-A transcription, as well as its importance on centromere function. [ABSTRACT FROM AUTHOR]
Titel: |
Cell Cycle-Regulated Transcription of CENP-A by the MBF Complex Ensures Optimal Level of CENP-A for Centromere Formation.
|
---|---|
Autor/in / Beteiligte Person: | Aristizabal-Corrales, David ; Yang, Jinpu ; Li, Fei |
Link: | |
Zeitschrift: | Genetics, Jg. 211 (2019-03-01), Heft 3, S. 861-875 |
Veröffentlichung: | 2019 |
Medientyp: | academicJournal |
ISSN: | 0016-6731 (print) |
DOI: | 10.1534/genetics.118.301745 |
Schlagwort: |
|
Sonstiges: |
|