A two-step mechanism for epigenetic specification of centromere identity and function
Daniele Fachinetti,H. Diego Folco,H. Diego Folco,Yael Nechemia-Arbely,Luis P. Valente,Kristen Nguyen,Alex J. Wong,Quan Zhu,Andrew J. Holland,Andrew J. Holland,Arshad Desai,Lars E.T. Jansen,Don W. Cleveland +12 more
TLDR
Using gene targeting in human cells and fission yeast, chromatin containing the centromere-specific histone H3 variant CENP-A is demonstrated to be the epigenetic mark that acts through a two-step mechanism to identify, maintain and propagateCentromere function indefinitely.Abstract:
The basic determinant of chromosome inheritance, the centromere, is specified in many eukaryotes by an epigenetic mark. Using gene targeting in human cells and fission yeast, chromatin containing the centromere-specific histone H3 variant CENP-A is demonstrated to be the epigenetic mark that acts through a two-step mechanism to identify, maintain and propagate centromere function indefinitely. Initially, centromere position is replicated and maintained by chromatin assembled with the centromere-targeting domain (CATD) of CENP-A substituted into H3. Subsequently, nucleation of kinetochore assembly onto CATD-containing chromatin is shown to require either the amino- or carboxy-terminal tail of CENP-A for recruitment of inner kinetochore proteins, including stabilizing CENP-B binding to human centromeres or direct recruitment of CENP-C, respectively.read more
Citations
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Journal ArticleDOI
A Molecular View of Kinetochore Assembly and Function.
Andrea Musacchio,Arshad Desai +1 more
TL;DR: A broad summary of progress in the elucidation of the composition of the kinetochore and the identification of various physical and functional modules within its substructure has led to a much deeper molecular understanding of kinetchore organization and the origins of its functional output.
Journal ArticleDOI
The molecular basis for centromere identity and function
TL;DR: Ongoing work is providing important molecular insights into the central requirements for centromere identity and propagation, and the mechanisms by which centromeres recruit kinetochores to connect to spindle microtubules.
Journal ArticleDOI
Variants of core histones and their roles in cell fate decisions, development and cancer
Marcus Buschbeck,Sandra B. Hake +1 more
TL;DR: Histone variants endow chromatin with unique properties and show a specific genomic distribution that is regulated by specific deposition and removal machineries, and these alterations promote or even drive cancer development through mechanisms that involve changes in epigenetic plasticity, genomic stability and senescence.
Journal ArticleDOI
The quantitative architecture of centromeric chromatin
Dani L. Bodor,João F. Mata,Mikhail Sergeev,Mikhail Sergeev,Ana Filipa David,Kevan J. Salimian,Tanya Panchenko,Don W. Cleveland,Don W. Cleveland,Ben E. Black,Jagesh V. Shah,Jagesh V. Shah,Lars E.T. Jansen +12 more
TL;DR: A quantitative view of the centromere is presented that provides a mechanistic framework for both robust epigenetic inheritance of centromeres and the paucity of neocentromere formation.
Journal ArticleDOI
DNA Sequence-Specific Binding of CENP-B Enhances the Fidelity of Human Centromere Function
Daniele Fachinetti,Joo Seok Han,Moira A. McMahon,Peter Ly,Amira Abdullah,Alex J. Wong,Don W. Cleveland +6 more
TL;DR: DNA sequence-dependent binding of CENP-B within α-satellite repeats is required to stabilize optimal centromeric levels of C ENP-C, and data demonstrate a DNA sequence-specific enhancement by CENp-B of the fidelity of epigenetically defined human centromere function.
References
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Book ChapterDOI
Molecular genetic analysis of fission yeast Schizosaccharomyces pombe.
TL;DR: This chapter describes techniques concerned with classical and molecular genetics, cell biology, and biochemistry that can be used with Schizosaccharomyces pombe.
Journal ArticleDOI
The Conserved KMN Network Constitutes the Core Microtubule-Binding Site of the Kinetochore
TL;DR: It is proposed that the conserved KNL-1/Mis12 complex/Ndc80 complex (KMN) network constitutes the core microtubule-binding site of the kinetochore.
Journal ArticleDOI
Centromeres and Kinetochores: From Epigenetics to Mitotic Checkpoint Signaling
TL;DR: Efforts to understand the nature and specification of the centromere have demonstrated that this central element for ensuring inheritance is itself epigenetically determined.
Journal ArticleDOI
Identification of a family of human centromere proteins using autoimmune sera from patients with scleroderma.
TL;DR: Examination of “preimmune” serum samples from a patient who progressively developed the symptoms of scleroderma CREST over a period of several years shows that these patients make antibody species recognizing at least three distinct epitopes on C ENP-B and two on CENP-C.
Journal ArticleDOI
The human CENP-A centromeric nucleosome-associated complex
Daniel R. Foltz,Lars E.T. Jansen,Ben E. Black,Aaron O. Bailey,John R. Yates,Don W. Cleveland +5 more
TL;DR: It is shown that CENP-A nucleosomes directly recruit a proximal CEN parenthood-associated nucleosome associated complex (NAC) comprised of three new human centromere proteins (CENp-M, CenP-N and CENT-T), along with C ENP-U(50), CEN P-C and C ENp-H.