Abstract
ABSTRACTCENP-B binds to CENP-B boxes on centromeric satellite DNAs (known as alphoid DNA in humans). CENP-B maintains kinetochore function through interactions with CENP-A nucleosomes and CENP-C. CENP-B binding to transfected alphoid DNA can induce de novo CENP-A assembly, functional centromere and kinetochore formation, and subsequent human artificial chromosome (HAC) formation. Furthermore, CENP-B also facilitates H3K9 (histone H3 lysine 9) trimethylation on alphoid DNA, mediated by Suv39h1, at ectopic alphoid DNA integration sites. Excessive heterochromatin invasion into centromere chromatin suppresses CENP-A assembly. It is unclear how CENP-B controls such different chromatin states. Here, we show that the CENP-B acidic domain recruits histone chaperones and many chromatin modifiers, including the H3K36 methylase ASH1L, as well as the heterochromatin components Suv39h1 and HP1 (HP1α, β and γ, also known as CBX5, CBX1 and CBX3, respectively). ASH1L facilitates the formation of open chromatin competent for CENP-A assembly on alphoid DNA. These results indicate that CENP-B is a nexus for histone modifiers that alternatively promote or suppress CENP-A assembly by mutually exclusive mechanisms. Besides the DNA-binding domain, the CENP-B acidic domain also facilitates CENP-A assembly de novo on transfected alphoid DNA. CENP-B therefore balances CENP-A assembly and heterochromatin formation on satellite DNA.
Highlights
The centromere is a specialized genetic locus that plays an essential role in chromosome segregation
We screened for factors that assemble at the ectopic alphoidtetO DNA integration site
In addition to the N-terminal DNA-binding domain, which can bind to CENP-A nucleosomes (Fujita et al, 2015; Fachinetti et al, 2015), the CENPB acidic domain facilitated assembly of the H3K36 methyltransferase ASH1L, thereby inducing an open chromatin state competent for CENP-A assembly or exchange
Summary
The centromere is a specialized genetic locus that plays an essential role in chromosome segregation. Handling Editor: David Glover Received 23 December 2019; Accepted 29 June 2020 the specific histone H3 variant CENP-A (Earnshaw and Rothfield, 1985; Palmer et al, 1987; Black and Cleveland, 2011), an epigenetic mark that directs the assembly of other centromere proteins (for example, the constitutive centromere-associated network, CCAN, or the interphase centromere complex, ICEN) and outer kinetochore components (Foltz et al, 2006; Izuta et al, 2006; Okada et al, 2006; Allshire and Karpen, 2008; Cheeseman and Desai, 2008; Fukagawa and Earnshaw, 2014; Westhorpe and Straight, 2015; Musacchio and Desai, 2017). The modification status of centromeric histones is important for CENP-A assembly (Bergmann et al, 2011; Shang et al, 2016). Methylation of histone H3 lysine 4 (H3K4me) and lysine 36 (H3K36me) is observed around CENP-A chromatin (Sullivan and Karpen, 2004; Bergmann et al, 2011; Bailey et al, 2016). Dimethylation of H3K4 (H3K4me2) is required for the recruitment of HJURP (Bergmann et al, 2011) and for preventing flanking heterochromatin from spreading into the centromere (Molina et al, 2016)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
