Interaction between HP1α and replication proteins in mammalian cells

Auth, Tanja; Kunkel, E.; Grummt, Friedrich

doi:10.1016/j.yexcr.2006.07.014

Cited by 44 publications

(39 citation statements)

References 61 publications

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“…Immunofluorescence studies showed that human and mouse Orc2 localizes in a cell cycle-regulated manner to many diffuse foci in the nucleus, HP1-containing heterochromatic loci, and centrosomes and centromeres ( Fig. 1 B'-D') (11,15,20,21,30). In addition to Orc2, other ORC subunits including Orc1, Orc3, and Orc5 localize at the Orc2-and HP1-associated heterochromatin in MCF7 cells (Fig.…”

Section: Resultsmentioning

confidence: 95%

“…In addition to their role in DNA replication, ORC subunits have also been implicated in transcriptional gene silencing in Saccharomyces cerevisiae (10), heterochromatin formation in Drosophila, mouse, and humans (11)(12)(13)(14)(15), sister chromatid cohesion in S. cerevisiae, Schizosaccharomyces pombe, and Xenopus (16-18), ribosome biogenesis (19), centrosome biology in human and mouse (15,20,21), mitotic chromosome function in human and Xenopus (15,22,23), cytokinesis in human cells and Drosophila (24,25), regulation of dendrite development in postmitotic neurons (26), and neural transmission and synaptic function in Drosophila (27) (see reviews in refs. 28,29).…”

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confidence: 99%

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Human origin recognition complex is essential for HP1 binding to chromatin and heterochromatin organization

Prasanth

Shen

Prasanth

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

130

146

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The origin recognition complex (ORC) is a DNA replication initiator protein also known to be involved in diverse cellular functions including gene silencing, sister chromatid cohesion, telomere biology, heterochromatin localization, centromere and centrosome activity, and cytokinesis. We show that, in human cells, multiple ORC subunits associate with hetereochromatin protein 1 (HP1) α-and HP1β-containing heterochromatic foci. Fluorescent bleaching studies indicate that multiple subcomplexes of ORC exist at heterochromatin, with Orc1 stably associating with heterochromatin in G1 phase, whereas other ORC subunits have transient interactions throughout the cell-division cycle. Both Orc1 and Orc3 directly bind to HP1α, and two domains of Orc3, a coiled-coil domain and a mod-interacting region domain, can independently bind to HP1α; however, both are essential for in vivo localization of Orc3 to heterochromatic foci. Direct binding of both Orc1 and Orc3 to HP1 suggests that, after the degradation of Orc1 at the G1/S boundary, Orc3 facilitates assembly of ORC/HP1 proteins to chromatin. Although depletion of Orc2 and Orc3 subunits by siRNA caused loss of HP1α association to heterochromatin, loss of Orc1 and Orc5 caused aberrant HP1α distribution only to pericentric heterochromatin-surrounding nucleoli. Depletion of HP1α from human cells also shows loss of Orc2 binding to heterochromatin, suggesting that ORC and HP1 proteins are mutually required for each other to bind to heterochromatin. Similar to HP1α-depleted cells, Orc2 and Orc3 siRNA-treated cells also show loss of compaction at satellite repeats, suggesting that ORC together with HP1 proteins may be involved in organizing higherorder chromatin structure and centromere function.centromere | origin recognition complex | pericentric heterochromatin | chromatin structure

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Section: Resultsmentioning

confidence: 95%

mentioning

confidence: 99%

Human origin recognition complex is essential for HP1 binding to chromatin and heterochromatin organization

Prasanth

Shen

Prasanth

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

130

146

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“…For example, human and Drosophila ORC bind to HP1 (heterochromatin protein 1) (1)(2)(3)(4) and human ORC associates with telomeric and pericentromeric heterochromatin (5)(6)(7). Orc1 and the deacetylase Sir2 also repress genes near telomeres in the evolutionarily distant organism Plasmodium falciparum, which causes malaria (8).…”

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confidence: 99%

Transcriptional silencing functions of the yeast protein Orc1/Sir3 subfunctionalized after gene duplication

Hickman

Rusché

2010

Proc. Natl. Acad. Sci. U.S.A.

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The origin recognition complex (ORC) defines origins of replication and also interacts with heterochromatin proteins in a variety of species, but how ORC functions in heterochromatin assembly remains unclear. The largest subunit of ORC, Orc1, is particularly interesting because it contains a nucleosome-binding BAH domain and because it gave rise to Sir3, a key silencing protein in Saccharomyces cerevisiae, through gene duplication. We examined whether Orc1 possessed a Sir3-like silencing function before duplication and found that Orc1 from the yeast Kluyveromyces lactis, which diverged from S. cerevisiae before the duplication, acts in conjunction with the deacetylase Sir2 and the histone-binding protein Sir4 to generate heterochromatin at telomeres and a matingtype locus. Moreover, the ability of KlOrc1 to spread across a silenced locus depends on its nucleosome-binding BAH domain and the deacetylase Sir2. Interestingly, KlOrc1 appears to act independently of the entire ORC, as other subunits of the complex, Orc4 and Orc5, are not strongly associated with silenced domains. These findings demonstrate that Orc1 functioned in silencing before duplication and suggest that Orc1 and Sir2, both of which are broadly conserved among eukaryotes, may have an ancient history of cooperating to generate chromatin structures, with Sir2 deacetylating histones and Orc1 binding to these deacetylated nucleosomes through its BAH domain.heterochromatin | replication | SIR

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“…In other eukaryotes we see no readily identifiable consensus sequence in origins of DNA replication (Mechali, 2010). Even so, strong links of ORC to gene silencing and heterochromatin have been identified by many studies in Schizosaccharomyces pombe and in higher eukaryotes (Pak et al, 1997;Auth et al, 2006;Deng et al, 2007;Stuermer et al, 2007;Kato et al, 2008;Deng et al, 2009;Prasanth et al, 2010). Perhaps ORC has evolved to lose its stringent sequence requirements for binding to DNA, but the origin-ORC module has maintained its flexibility and the ability to accommodate varying conformations.…”

Section: Resultsmentioning

confidence: 90%

The Silencing Face of DNA Replication: Gene Repression Mediated by DNA Replication Factors

Chisamore-Robert¹,

Jeffery²,

Yankulov³

2011

DNA Replication-Current Advances

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Interaction between HP1α and replication proteins in mammalian cells

Cited by 44 publications

References 61 publications

Human origin recognition complex is essential for HP1 binding to chromatin and heterochromatin organization

Human origin recognition complex is essential for HP1 binding to chromatin and heterochromatin organization

Transcriptional silencing functions of the yeast protein Orc1/Sir3 subfunctionalized after gene duplication

The Silencing Face of DNA Replication: Gene Repression Mediated by DNA Replication Factors

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