Truncated HP1 lacking a functional chromodomain induces heterochromatinization upon in vivo targeting

被引:16
作者
Brink, MC
van der Velden, Y
de Leeuw, W
Mateos-Langerak, J
Belmont, AS
van Driel, R
Verschure, PJ
机构
[1] Univ Amsterdam, Bioctr Amsterdam, Swammerdam Inst Life Sci, NL-1098 SM Amsterdam, Netherlands
[2] CWI, Ctr Math & Comp Sci, NL-1098 SJ Amsterdam, Netherlands
[3] Univ Illinois, Dept Cell & Struct Biol, Urbana, IL 61801 USA
关键词
large-scale chromatin structure; heterochromatin protein 1; histone methylation; gene expression; epigenetics;
D O I
10.1007/s00418-005-0088-7
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Packaging of the eukaryotic genome into higher order chromatin structures is tightly related to gene expression. Pericentromeric heterochromatin is typified by accumulations of heterochromatin protein 1 (HP1), methylation of histone H3 at lysine 9 (MeH3K9) and global histone deacetylation. HP1 interacts with chromatin by binding to MeH3K9 through the chromodomain (CD). HP1 dimerizes with itself and binds a variety of proteins through its chromoshadow domain. We have analyzed at the single cell level whether HP1 lacking its functional CD is able to induce heterochromatinization in vivo. We used a lac-operator array-based system in mammalian cells to target EGFP-lac repressor tagged truncated HP1 alpha and HP1 beta to a lac operator containing gene-amplified chromosome region in living cells. After targeting truncated HP1 alpha or HP1 beta we observe enhanced tri-MeH3K9 and recruitment of endogenous HP1 alpha and HP1 beta to the chromosome region. We show that CD-less HP1 alpha can induce chromatin condensation, whereas the effect of truncated HP1 beta is less pronounced. Our results demonstrate that after lac repressor-mediated targeting, HP1 alpha and HP1 beta without a functional CD are able to induce heterochromatinization.
引用
收藏
页码:53 / 61
页数:9
相关论文
共 34 条
  • [1] AASLAND R, 1995, NUCLEIC ACIDS RES, V23, P3168
  • [2] Mutations in the heterochromatin protein 1 (HP1) hinge domain affect HP1 protein interactions and chromosomal distribution
    Badugu, R
    Yoo, Y
    Singh, PB
    Kellum, R
    [J]. CHROMOSOMA, 2005, 113 (07) : 370 - 384
  • [3] Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain
    Bannister, AJ
    Zegerman, P
    Partridge, JF
    Miska, EA
    Thomas, JO
    Allshire, RC
    Kouzarides, T
    [J]. NATURE, 2001, 410 (6824) : 120 - 124
  • [4] Maintenance of stable heterochromatin domains by dynamic HP1 binding
    Cheutin, T
    McNairn, AJ
    Jenuwein, T
    Gilbert, DM
    Singh, PB
    Misteli, T
    [J]. SCIENCE, 2003, 299 (5607) : 721 - 725
  • [5] Heterochromatin, HP1 and methylation at lysine 9 of histone H3 in animals
    Cowell, IG
    Aucott, R
    Mahadevaiah, SK
    Burgoyne, PS
    Huskisson, N
    Bongiorni, S
    Prantera, G
    Fanti, L
    Pimpinelli, S
    Wu, R
    Gilbert, DM
    Shi, W
    Fundele, R
    Morrison, H
    Jeppesen, P
    Singh, PB
    [J]. CHROMOSOMA, 2002, 111 (01) : 22 - 36
  • [6] Heterochromatin structure and function
    Dillon, N
    [J]. BIOLOGY OF THE CELL, 2004, 96 (08) : 631 - 637
  • [7] Molecular biology: Chromatin higher order folding: Wrapping up transcription
    Horn, PJ
    Peterson, CL
    [J]. SCIENCE, 2002, 297 (5588) : 1824 - 1827
  • [8] M32, a murine homologue of Drosophila heterochromatin protein 1 (HP1), localises to euchromatin within interphase nuclei and is largely excluded from constitutive heterochromatin
    Horsley, D
    Hutchings, A
    Butcher, GW
    Singh, PB
    [J]. CYTOGENETICS AND CELL GENETICS, 1996, 73 (04): : 308 - 311
  • [9] Structure of HP1 chromodomain bound to a lysine 9-methylated histone H3 tail
    Jacobs, SA
    Khorasanizadeh, S
    [J]. SCIENCE, 2002, 295 (5562) : 2080 - 2083
  • [10] Specificity of the HP1 chromo domain for the methylated N-terminus of histone H3
    Jacobs, SA
    Taverna, SD
    Zhang, YN
    Briggs, SD
    Li, JM
    Eissenberg, JC
    Allis, CD
    Khorasanizadeh, S
    [J]. EMBO JOURNAL, 2001, 20 (18) : 5232 - 5241