Functional mammalian homologues of the Drosophila PEV-modifier Su(var)3-9 encode centromere-associated proteins which complex with the heterochromatin component M31

L Aagaard, G Laible, P Selenko, M Schmid, R Dorn, G Schotta, S Kuhfittig, A Wolf, A Lebersorger, P B Singh, G Reuter, T Jenuwein

Research output: Contribution to journalArticle

367 Citations (Scopus)

Abstract

The chromo and SET domains are conserved sequence motifs present in chromosomal proteins that function in epigenetic control of gene expression, presumably by modulating higher order chromatin. Based on sequence information from the SET domain, we have isolated human (SUV39H1) and mouse (Suv39h1) homologues of the dominant Drosophila modifier of position-effect-variegation (PEV) Su(var)3-9. Mammalian homologues contain, in addition to the SET domain, the characteristic chromo domain, a combination that is also preserved in the Schizosaccharyomyces pombe silencing factor clr4. Chromatin-dependent gene regulation is demonstrated by the potential of human SUV39H1 to increase repression of the pericentromeric white marker gene in transgenic flies. Immunodetection of endogenous Suv39h1/SUV39H1 proteins in a variety of mammalian cell lines reveals enriched distribution at heterochromatic foci during interphase and centromere-specific localization during metaphase. In addition, Suv39h1/SUV39H1 proteins associate with M31, currently the only other characterized mammalian SU(VAR) homologue. These data indicate the existence of a mammalian SU(VAR) complex and define Suv39h1/SUV39H1 as novel components of mammalian higher order chromatin.

Original languageEnglish
Pages (from-to)1923-38
Number of pages16
JournalEMBO Journal
Volume18
Issue number7
DOIs
Publication statusPublished - Apr 1 1999

Fingerprint

Chromosomal Position Effects
Heterochromatin
Centromere
Drosophila
Chromatin
Gene expression
Proteins
Conserved Sequence
Interphase
Metaphase
Epigenomics
Diptera
Genes
Cells
Gene Expression
Cell Line

Keywords

  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Base Sequence
  • Centromere
  • Chromosomal Proteins, Non-Histone
  • Conserved Sequence
  • DNA Primers
  • Drosophila
  • Drosophila Proteins
  • Fungal Proteins
  • Genes, Insect
  • Heterochromatin
  • Humans
  • Insect Proteins
  • Mice
  • Molecular Sequence Data
  • Repressor Proteins
  • Schizosaccharomyces
  • Sequence Homology, Amino Acid
  • Species Specificity
  • Journal Article
  • Research Support, Non-U.S. Gov't

Cite this

Functional mammalian homologues of the Drosophila PEV-modifier Su(var)3-9 encode centromere-associated proteins which complex with the heterochromatin component M31. / Aagaard, L; Laible, G; Selenko, P; Schmid, M; Dorn, R; Schotta, G; Kuhfittig, S; Wolf, A; Lebersorger, A; Singh, P B; Reuter, G; Jenuwein, T.

In: EMBO Journal, Vol. 18, No. 7, 01.04.1999, p. 1923-38.

Research output: Contribution to journalArticle

Aagaard, L, Laible, G, Selenko, P, Schmid, M, Dorn, R, Schotta, G, Kuhfittig, S, Wolf, A, Lebersorger, A, Singh, PB, Reuter, G & Jenuwein, T 1999, 'Functional mammalian homologues of the Drosophila PEV-modifier Su(var)3-9 encode centromere-associated proteins which complex with the heterochromatin component M31', EMBO Journal, vol. 18, no. 7, pp. 1923-38. https://doi.org/10.1093/emboj/18.7.1923
Aagaard, L ; Laible, G ; Selenko, P ; Schmid, M ; Dorn, R ; Schotta, G ; Kuhfittig, S ; Wolf, A ; Lebersorger, A ; Singh, P B ; Reuter, G ; Jenuwein, T. / Functional mammalian homologues of the Drosophila PEV-modifier Su(var)3-9 encode centromere-associated proteins which complex with the heterochromatin component M31. In: EMBO Journal. 1999 ; Vol. 18, No. 7. pp. 1923-38.
@article{dc215348c5024b0eb567562fe9c03485,
title = "Functional mammalian homologues of the Drosophila PEV-modifier Su(var)3-9 encode centromere-associated proteins which complex with the heterochromatin component M31",
abstract = "The chromo and SET domains are conserved sequence motifs present in chromosomal proteins that function in epigenetic control of gene expression, presumably by modulating higher order chromatin. Based on sequence information from the SET domain, we have isolated human (SUV39H1) and mouse (Suv39h1) homologues of the dominant Drosophila modifier of position-effect-variegation (PEV) Su(var)3-9. Mammalian homologues contain, in addition to the SET domain, the characteristic chromo domain, a combination that is also preserved in the Schizosaccharyomyces pombe silencing factor clr4. Chromatin-dependent gene regulation is demonstrated by the potential of human SUV39H1 to increase repression of the pericentromeric white marker gene in transgenic flies. Immunodetection of endogenous Suv39h1/SUV39H1 proteins in a variety of mammalian cell lines reveals enriched distribution at heterochromatic foci during interphase and centromere-specific localization during metaphase. In addition, Suv39h1/SUV39H1 proteins associate with M31, currently the only other characterized mammalian SU(VAR) homologue. These data indicate the existence of a mammalian SU(VAR) complex and define Suv39h1/SUV39H1 as novel components of mammalian higher order chromatin.",
keywords = "Amino Acid Sequence, Animals, Animals, Genetically Modified, Base Sequence, Centromere, Chromosomal Proteins, Non-Histone, Conserved Sequence, DNA Primers, Drosophila, Drosophila Proteins, Fungal Proteins, Genes, Insect, Heterochromatin, Humans, Insect Proteins, Mice, Molecular Sequence Data, Repressor Proteins, Schizosaccharomyces, Sequence Homology, Amino Acid, Species Specificity, Journal Article, Research Support, Non-U.S. Gov't",
author = "L Aagaard and G Laible and P Selenko and M Schmid and R Dorn and G Schotta and S Kuhfittig and A Wolf and A Lebersorger and Singh, {P B} and G Reuter and T Jenuwein",
year = "1999",
month = "4",
day = "1",
doi = "10.1093/emboj/18.7.1923",
language = "English",
volume = "18",
pages = "1923--38",
journal = "EMBO Journal",
issn = "0261-4189",
publisher = "Nature Publishing Group",
number = "7",

}

TY - JOUR

T1 - Functional mammalian homologues of the Drosophila PEV-modifier Su(var)3-9 encode centromere-associated proteins which complex with the heterochromatin component M31

AU - Aagaard, L

AU - Laible, G

AU - Selenko, P

AU - Schmid, M

AU - Dorn, R

AU - Schotta, G

AU - Kuhfittig, S

AU - Wolf, A

AU - Lebersorger, A

AU - Singh, P B

AU - Reuter, G

AU - Jenuwein, T

PY - 1999/4/1

Y1 - 1999/4/1

N2 - The chromo and SET domains are conserved sequence motifs present in chromosomal proteins that function in epigenetic control of gene expression, presumably by modulating higher order chromatin. Based on sequence information from the SET domain, we have isolated human (SUV39H1) and mouse (Suv39h1) homologues of the dominant Drosophila modifier of position-effect-variegation (PEV) Su(var)3-9. Mammalian homologues contain, in addition to the SET domain, the characteristic chromo domain, a combination that is also preserved in the Schizosaccharyomyces pombe silencing factor clr4. Chromatin-dependent gene regulation is demonstrated by the potential of human SUV39H1 to increase repression of the pericentromeric white marker gene in transgenic flies. Immunodetection of endogenous Suv39h1/SUV39H1 proteins in a variety of mammalian cell lines reveals enriched distribution at heterochromatic foci during interphase and centromere-specific localization during metaphase. In addition, Suv39h1/SUV39H1 proteins associate with M31, currently the only other characterized mammalian SU(VAR) homologue. These data indicate the existence of a mammalian SU(VAR) complex and define Suv39h1/SUV39H1 as novel components of mammalian higher order chromatin.

AB - The chromo and SET domains are conserved sequence motifs present in chromosomal proteins that function in epigenetic control of gene expression, presumably by modulating higher order chromatin. Based on sequence information from the SET domain, we have isolated human (SUV39H1) and mouse (Suv39h1) homologues of the dominant Drosophila modifier of position-effect-variegation (PEV) Su(var)3-9. Mammalian homologues contain, in addition to the SET domain, the characteristic chromo domain, a combination that is also preserved in the Schizosaccharyomyces pombe silencing factor clr4. Chromatin-dependent gene regulation is demonstrated by the potential of human SUV39H1 to increase repression of the pericentromeric white marker gene in transgenic flies. Immunodetection of endogenous Suv39h1/SUV39H1 proteins in a variety of mammalian cell lines reveals enriched distribution at heterochromatic foci during interphase and centromere-specific localization during metaphase. In addition, Suv39h1/SUV39H1 proteins associate with M31, currently the only other characterized mammalian SU(VAR) homologue. These data indicate the existence of a mammalian SU(VAR) complex and define Suv39h1/SUV39H1 as novel components of mammalian higher order chromatin.

KW - Amino Acid Sequence

KW - Animals

KW - Animals, Genetically Modified

KW - Base Sequence

KW - Centromere

KW - Chromosomal Proteins, Non-Histone

KW - Conserved Sequence

KW - DNA Primers

KW - Drosophila

KW - Drosophila Proteins

KW - Fungal Proteins

KW - Genes, Insect

KW - Heterochromatin

KW - Humans

KW - Insect Proteins

KW - Mice

KW - Molecular Sequence Data

KW - Repressor Proteins

KW - Schizosaccharomyces

KW - Sequence Homology, Amino Acid

KW - Species Specificity

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1093/emboj/18.7.1923

DO - 10.1093/emboj/18.7.1923

M3 - Article

C2 - 10202156

VL - 18

SP - 1923

EP - 1938

JO - EMBO Journal

JF - EMBO Journal

SN - 0261-4189

IS - 7

ER -