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Mitotic centromeric targeting of HP1 and its binding to Sgo1 are dispensable for sister-chromatid cohesion in human cells

Journal Article · · Molecular Biology of the Cell
 [1];  [2];  [2];  [2];  [3];  [2]
  1. Univ. of Texas Southwestern Medical Center, Dallas, TX (United States). Howard Hughes Medical Inst. Dept. of Pharmacology; DOE/OSTI
  2. Univ. of Texas Southwestern Medical Center, Dallas, TX (United States). Howard Hughes Medical Inst. Dept. of Pharmacology
  3. Univ. of Texas Southwestern Medical Center, Dallas, TX (United States). Dept. of Biochemistry
Human Shugoshin 1 (Sgo1) protects centromeric sister-chromatid cohesion during prophase and prevents premature sister-chromatid separation. Heterochromatin protein 1 (HP1) has been proposed to protect centromeric sister-chromatid cohesion by directly targeting Sgo1 to centromeres in mitosis. Here we show that HP1α is targeted to mitotic centromeres by INCENP, a subunit of the chromosome passenger complex (CPC). Biochemical and structural studies show that both HP1–INCENP and HP1–Sgo1 interactions require the binding of the HP1 chromo shadow domain to PXVXL/I motifs in INCENP or Sgo1, suggesting that the INCENP-bound, centromeric HP1α is incapable of recruiting Sgo1. Consistently, a Sgo1 mutant deficient in HP1 binding is functional in centromeric cohesion protection and localizes normally to centromeres in mitosis. By contrast, INCENP or Sgo1 mutants deficient in HP1 binding fail to localize to centromeres in interphase. Therefore, our results suggest that HP1 binding by INCENP or Sgo1 is dispensable for centromeric cohesion protection during mitosis of human cells, but might regulate yet uncharacterized interphase functions of CPC or Sgo1 at the centromeres.
Research Organization:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
Grant/Contract Number:
AC02-06CH11357
OSTI ID:
1625225
Alternate ID(s):
OSTI ID: 1869837
OSTI ID: 1872635
Journal Information:
Molecular Biology of the Cell, Journal Name: Molecular Biology of the Cell Journal Issue: 8 Vol. 22; ISSN 1059-1524
Publisher:
American Society for Cell BiologyCopyright Statement
Country of Publication:
United States
Language:
English

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Cited By (21)

Cell division: control of the chromosomal passenger complex in time and space journal October 2013
Bub1 targeting to centromeres is sufficient for Sgo1 recruitment in the absence of kinetochores journal April 2016
Liquid droplet formation by HP1α suggests a role for phase separation in heterochromatin journal June 2017
Multivalency governs HP1α association dynamics with the silent chromatin state journal June 2015
NBS1 interacts with HP1 to ensure genome integrity journal December 2019
Aurora kinase B-phosphorylated HP1α functions in chromosomal instability journal May 2019
Strong epigenetic similarity between maize centromeric and pericentromeric regions at the level of small RNAs, DNA methylation and H3 chromatin modifications journal November 2011
Epigenetic Control of Effector Gene Expression in the Plant Pathogenic Fungus Leptosphaeria maculans journal March 2014
The chromosomal passenger complex (CPC): from easy rider to the godfather of mitosis journal November 2012
Aurora A-dependent CENP-A phosphorylation at inner centromeres protects bioriented chromosomes against cohesion fatigue journal May 2018
Peptide recognition by heterochromatin protein 1 (HP1) chromoshadow domains revisited: Plasticity in the pseudosymmetric histone binding site of human HP1 journal April 2017
Aurora B kinase activity–dependent and –independent functions of the chromosomal passenger complex in regulating sister chromatid cohesion journal February 2019
The expanding phenotypes of cohesinopathies: one ring to rule them all! journal September 2019
Priming chromatin for segregation: functional roles of mitotic histone modifications journal January 2020
Mitotic phosphorylation of HP1α regulates its cell cycle-dependent chromatin binding journal December 2018
HP 1α targets the chromosomal passenger complex for activation at heterochromatin before mitotic entry journal February 2018
HP 1 links centromeric heterochromatin to centromere cohesion in mammals journal February 2018
Heterochromatin and cohesion protection at human centromeres: the final say of a long controversy? journal March 2018
The Drosophila histone variant H2A.V works in concert with HP1 to promote kinetochore-driven microtubule formation journal February 2015
Phosphorylation–dephosphorylation cycle of HP1α governs accurate mitotic progression journal April 2014
The Drosophila histone variant H2A.V works in concert with HP1 to promote kinetochore-driven microtubule formation. text January 2015

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