Heterochromatin protein 1: Difference between revisions

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{{protein
{{infobox protein
| Name = chromobox homolog 5
| Name = [[CBX5 (gene)|chromobox homolog 5]]
| caption =  
| caption =  
| image =  
| image =  
| width =  
| width =  
| HGNCid = 1555
| HGNCid = 1555
| Symbol = CBX5
| Symbol = [[CBX5 (gene)|CBX5]]
| AltSymbols = HP1-alpha
| AltSymbols = HP1-alpha
| EntrezGene = 23468
| EntrezGene = 23468
Line 18: Line 18:
| LocusSupplementaryData =  
| LocusSupplementaryData =  
}}
}}
{{protein
{{infobox protein
| Name = chromobox homolog 1
| Name = [[CBX1|chromobox homolog 1]]
| caption =  
| caption =  
| image =  
| image =  
| width =  
| width =  
| HGNCid = 1551
| HGNCid = 1551
| Symbol = CBX1
| Symbol = [[CBX1]]
| AltSymbols = HP1-beta
| AltSymbols = HP1-beta
| EntrezGene = 10951
| EntrezGene = 10951
Line 37: Line 37:
| LocusSupplementaryData =  
| LocusSupplementaryData =  
}}
}}
{{protein
{{infobox protein
| Name = chromobox homolog 3
| Name = [[CBX3|chromobox homolog 3]]
| caption =  
| caption =  
| image =  
| image =  
| width =  
| width =  
| HGNCid = 1553
| HGNCid = 1553
| Symbol = CBX3
| Symbol = [[CBX3]]
| AltSymbols = HP1-gamma
| AltSymbols = HP1-gamma
| EntrezGene = 11335
| EntrezGene = 11335
Line 57: Line 57:
}}
}}


The family of '''Heterochromatin Protein 1''' (HP1)  ("Chromobox Homolog", CBX) are highly conserved adapter molecules, which have important functions in the [[cell nucleus]]. These functions include gene repression by heterochromatin formation, transcriptional activation, regulation of binding of cohesin complexes to centromere, sequesteration of genes to nuclear periphery, transcriptional arrest,  maintenance of heterochromatin integrity, gene repression at single nucleosome level and gene repression by heterochromatization of euchromatin. HP1 [[protein]]s are fundamental units of [[heterochromatin]] packaging that are enriched at the [[centromere]]s and [[telomere]]s of nearly all Eukaryotic [[chromosome]]s with the notable exception of [[budding yeast]], in which a yeast-specific silencing complex of SIR (silent information regulatory) proteins are in action. Members of the HP1 family are characterized by two conserved domains: an N-terminal [[chromodomain]] and a C-terminal [[chromoshadow]] domain, which are separated by an Hinge Region in between. HP1 is also found at euchromatic sites, where its binding correlates with the repression of an increasing number of genes. HP1 was originally discovered in 1986 as an important factor in the phenomenon known as [[position effect variegation]] in [[Drosophila melanogaster]].<ref>
The family of '''heterochromatin protein 1''' ('''HP1''')  ("Chromobox Homolog", CBX) consists of highly conserved [[protein]]s, which have important functions in the [[cell nucleus]]. These functions include [[gene repression]] by [[heterochromatin]] formation, [[Transcription (genetics)|transcriptional]] activation, regulation of binding of cohesion complexes to centromeres, sequesteration of genes to nuclear periphery, transcriptional arrest,  maintenance of heterochromatin integrity, gene repression at the single nucleosome level and gene repression by heterochromatization of [[euchromatin]]. HP1 [[protein]]s are fundamental units of [[heterochromatin]] packaging that are enriched at the [[centromere]]s and [[telomere]]s of nearly all [[Eukaryote|Eukaryotic]] [[chromosome]]s with the notable exception of [[budding yeast]], in which a yeast-specific silencing complex of SIR (silent information regulatory) proteins serve a similar function. Members of the HP1 family are characterized by an N-terminal [[chromodomain]] and a C-terminal [[chromoshadow]] domain, separated by a Hinge region. HP1 is also found at euchromatic sites, where its binding correlates with [[gene repression]]. HP1 was originally discovered by Tharappel C James and [[Sarah Elgin]] in 1986 as a factor in the phenomenon known as [[position effect variegation]] in ''[[Drosophila melanogaster]]''.<ref>
{{cite journal
{{cite journal
|author=James, T.C. & S.C Elgin
|author1=James, T.C. |author2=S.C Elgin
|title=Identification of a nonhistone chromosomal protein associated with heterochromatin in Drosophila melanogaster and its gene
|title=Identification of a nonhistone chromosomal protein associated with heterochromatin in Drosophila melanogaster and its gene
|journal=Mol. Cell Biol.
|journal=Mol. Cell. Biol.
|year=1986
|year=1986
|volume=6
|volume=6
|pages=3862-3872}}
|pages=3862–3872
|pmid=3099166
|issue=11
|pmc=367149
}}
</ref><ref>
</ref><ref>
{{cite journal
{{cite journal
|author=Eissenberg, J.C., James, T.C., Foster-Hartnett, D.M., Hartnett, T., Ngan, V.K.W., Craig, C., Elgin, S.C.R.
|author=Eissenberg, J.C., James, T.C., Foster-Hartnett, D.M., Hartnett, T., Ngan, V.K.W., Craig, C., Elgin, S.C.R.
|year=1990
|year=1990
|title=Mutation in a heterochromatin-specific chromosomal protein are associated with suppression of position-effect variegation in ''D. melanogaster''
|title=Mutation in a heterochromatin-specific chromosomal protein is associated with suppression of position-effect variegation in Drosophila melanogaster
|journal=J. Cell Biol.
|journal=Proceedings of the National Academy of Sciences of the United States of America
|volume=111
|volume=87
|issue=5/2
|issue=24
|pages=5a}}</ref>
|pages=9923–7
|pmid=2124708
|pmc=55286
|doi=10.1073/pnas.87.24.9923
}}</ref>


==Isoforms==
== Paralogs and orthologs ==
Three different isoforms of HP1 are found in Drosophila melanogaster, HP1a, HP1b and HP1c. Subsequently homologues of HP1 were also discovered in [[S. pombe]] (Swi6), [[Xenopus]] (Xhp1α and Xhp1γ) and [[Chicken]] (CHCB1, CHCB2 and CHCB3). In mammals,<ref>
Three different [[Homology (biology)#Paralogy|paralogs]] of HP1 are found in Drosophila melanogaster, HP1a, HP1b and HP1c. Subsequently [[Homology (biology)#Orthology|orthologs]] of HP1 were also discovered in [[Schizosaccharomyces pombe|S. pombe]] (Swi6), [[Xenopus]] (Xhp1α and Xhp1γ) and [[Chicken]] (CHCB1, CHCB2 and CHCB3). In mammals,<ref>
{{cite journal
{{cite journal
|author=Singh PB, Miller JR, Pearce J, Kothary R, Burton RD, Paro R, James TC, Gaunt SJ.
|author1=Singh PB |author2=Miller JR |author3=Pearce J |author4=Kothary R |author5=Burton RD |author6=Paro R |author7=James TC |author8=Gaunt SJ. |title=A sequence motif found in a Drosophila heterochromatin protein is conserved in animals and plants
|title=A sequence motif found in a Drosophila heterochromatin protein is conserved in animals and plants
|journal=Nucleic Acids Res.
|journal=Nucleic Acids Res.
|year=1991
|date=February 1991
|month=Feb
|volume=19
|volume=19
|issue=4
|issue=4
|pages=789-94}}
|pages=789–94
</ref> there are three isoforms termed HP1α, HP1β and HP1γ each encoded by different genes.
|pmid=1708124
 
|doi=10.1093/nar/19.4.789
===HP1β===
|pmc=333712
}}
</ref> there are three [[Homology (biology)#Paralogy|paralogs]]: [[CBX5 (gene)|HP1α]], [[CBX1|HP1β]] and [[CBX3|HP1γ]]. In ''Arabidopsis thaliana'' (a plant), there is one homolog: LIKE HETEROCHROMATIN PROTEIN 1 (LHP1), also known as TERMINAL FLOWER 2 (TFL2).<ref>{{Cite journal|last=Kotake|first=Toshihisa|last2=Takada|first2=Shinobu|last3=Nakahigashi|first3=Kenji|last4=Ohto|first4=Masaaki|last5=Goto|first5=Koji|date=2003-06-15|title=Arabidopsis TERMINAL FLOWER 2 Gene Encodes a Heterochromatin Protein 1 Homolog and Represses both FLOWERING LOCUS T to Regulate Flowering Time and Several Floral Homeotic Genes|url=http://pcp.oxfordjournals.org/content/44/6/555|journal=Plant and Cell Physiology|language=en|volume=44|issue=6|pages=555–564|doi=10.1093/pcp/pcg091|issn=0032-0781|pmid=12826620}}</ref>


HP1β interacts with the Histon-[[Methyltransferase]] (HMTase) Suv(3)9h1 and is a component of both pericentric and telomeric [[heterochromatin]].<ref>
===HP1β in mammals===
{{main article|CBX1}}
HP1β interacts with the [[histone methyltransferase]] (HMTase) Suv(3-9)h1 and is a component of both pericentric and telomeric [[heterochromatin]].<ref>
{{cite journal
{{cite journal
|author=Aagaard L, Laible G, Selenko P, Schmid M, Dorn R, Schotta G, Kuhfittig S, Wolf A, Lebersorger A, Singh PB, Reuter G, Jenuwein T. |title=Functional mammalian homologues of the Drosophila PEV-modifier Su(var)3-9 encode centromere-associated proteins which complex with the heterochromatin component M31.
|vauthors=Aagaard L, Laible G, Selenko P, Schmid M, Dorn R, Schotta G, Kuhfittig S, Wolf A, Lebersorger A, Singh PB, Reuter G, Jenuwein T |title=Functional mammalian homologues of the Drosophila PEV-modifier Su(var)3-9 encode centromere-associated proteins which complex with the heterochromatin component M31
|journal=EMBO J.
|journal=EMBO J.
|year=1999
|date=April 1999
|month=Apr
|volume=18
|volume=18
|issue=7
|issue=7
|pages=1923-38}}
|pages=1923–38
|pmid=10202156 |doi=10.1093/emboj/18.7.1923
|pmc=1171278
}}
</ref><ref>
</ref><ref>
{{cite journal
{{cite journal
|author=Wreggett KA, Hill F, James PS, Hutchings A, Butcher GW, Singh PB
|vauthors=Wreggett KA, Hill F, James PS, Hutchings A, Butcher GW, Singh PB |title=A mammalian homologue of Drosophila heterochromatin protein 1 (HP1) is a component of constitutive heterochromatin
|title=A mammalian homologue of Drosophila heterochromatin protein 1 (HP1) is a component of constitutive heterochromatin
|journal=Cytogenet. Cell Genet.
|journal=Cytogenet. Cell Genet.
|year=1994
|year=1994
|volume=66
|volume=66
|issue=2
|issue=2
|pages=99-103}}
|pages=99–103
|pmid=8287692
|doi=10.1159/000133676
}}
</ref><ref>
</ref><ref>
{{cite journal
{{cite journal
|author=Sharma GG, Hwang KK, Pandita RK, Gupta A, Dhar S, Parenteau J, Agarwal M, Worman HJ, Wellinger RJ, Pandita TK.
|author1=Sharma GG |author2=Hwang KK |author3=Pandita RK |author4=Gupta A |author5=Dhar S |author6=Parenteau J |author7=Agarwal M |author8=Worman HJ |author9=Wellinger RJ |author10=Pandita TK. |title=Human Heterochromatin Protein 1 Isoforms HP1Hsα and HP1Hsβ Interfere with hTERT-Telomere Interactions and Correlate with Changes in Cell Growth and Response to Ionizing Radiation
|title=Human heterochromatin protein 1 isoforms HP1(Hsalpha) and HP1(Hsbeta) interfere with hTERT-telomere interactions and correlate with changes in cell growth and response to ionizing radiation
|journal=Mol. Cell. Biol.
|journal=Mol. Cell Biol.
|date=Nov 2003
|year=2003
|month=Nov;
|volume=23
|volume=23
|issue=22
|issue=22
|pages=8363-76}}
|pages=8363–76
|pmid=14585993
|doi=10.1128/MCB.23.22.8363-8376.2003
|pmc=262350
}}
</ref> HP1β is a dosage-dependent modifier of pericentric heterochromatin-induced silencing<ref>
</ref> HP1β is a dosage-dependent modifier of pericentric heterochromatin-induced silencing<ref>
{{cite journal
{{cite journal
|author=Festenstein R, Sharghi-Namini S, Fox M, Roderick K, Tolaini M, Norton T, Saveliev A, Kioussis D, Singh P
|vauthors=Festenstein R, Sharghi-Namini S, Fox M, Roderick K, Tolaini M, Norton T, Saveliev A, Kioussis D, Singh P |title=Heterochromatin protein 1 modifies mammalian PEV in a dose- and chromosomal-context-dependent manner
|title=Heterochromatin protein 1 modifies mammalian PEV in a dose- and chromosomal-context-dependent manner
|journal=Nat. Genet.
|journal=Nat. Genet.
|year=1999
|date=December 1999
|month=Dec
|volume=23
|volume=23
|issue=4
|issue=4
|pages=457-61}}
|pages=457–61
|pmid=10581035
|doi=10.1038/70579
}}
</ref> and silencing is thought to involve a dynamic association of the HP1β [[chromodomain]] with the tri-methylated [[Histone H3]] Me(3)K9H3.
</ref> and silencing is thought to involve a dynamic association of the HP1β [[chromodomain]] with the tri-methylated [[Histone H3]] Me(3)K9H3.


==HP1 Interacting Proteins==
==Interacting proteins==
HP1 seems to interact with numerous other proteins/molecules with different cellular functions in different organisms. Some of these HP1 interacting partners are: [[Histone H1]], [[Histone H3]], Methylated K9 [[Histone H3]], [[Histone H4]], [[Histone methyltransferase]], [[DNA methyltransferase]].
HP1 seems to interact with numerous other proteins/molecules with different cellular functions in different organisms. Some of these HP1 interacting partners are: [[histone H1]], [[histone H3]], methylated K9 [[histone H3]], [[histone H4]], [[histone methyltransferase]], [[DNA methyltransferase]], [[MECP2|methyl CpG binding protein MeCP2]], and the [[origin recognition complex]] protein ORC2


== Binding affinity and cooperativity ==
HP1 binding affinity to nucleosomes containing histone H3 methylated at lysine K9 is higher than to those with unmethylated lysine K9. HP1 binds [[nucleosomes]] as a dimer and in principle can form multimeric complexes. Some studies have interpreted HP1 binding in terms of nearest-neighbor [[cooperative binding]]. This mode of chromatin interactions could potentially lead to spreading of HP1 along the nucleosome chain. However, the analysis of available data on HP1 binding to nucleosomal arrays ''in vitro'' shows that experimental HP1 binding isotherms can be explained by a simple model without cooperative interactions between neighboring HP1 dimers.<ref>
{{cite journal
|author1=Teif V.B. |author2=Kepper N. |author3=Yserentant K |author4=Wedemann G. |author5=Rippe K. |title=Affinity, stoichiometry and cooperativity of heterochromatin protein 1 (HP1) binding to nucleosomal arrays
|journal=J. Phys.: Condens. Matter
|arxiv=1408.6184}}
</ref>


==See also==
==See also==
*[[Epigenetics]]
*[[Epigenetics]]
*[[nucleosome]]
*[[Heterochromatin]]
*[[Heterochromatin]]


==References==
==References==
{{reflist|2}}
{{reflist}}


Singh PB, Georgatos SD. HP1: facts, open questions, and speculation. J Struct Biol. 2002 Oct-Dec;140(1-3):10-6. Review
==Further reading==
*{{cite journal |vauthors=Singh PB, Georgatos SD |title=HP1: facts, open questions, and speculation |journal=J. Struct. Biol. |volume=140 |issue=1–3 |pages=10–6 |date=Oct–Dec 2002 |pmid=12490149 |doi=10.1016/S1047-8477(02)00536-1}} Review


{{Transcription factors}}
[[Category:Transcription factors]]
[[Category:Epigenetics]]
[[Category:Epigenetics]]
[[de:Heterochromatin Protein 1]]
{{WikiDoc Sources}}

Revision as of 04:29, 13 August 2017

chromobox homolog 5
Identifiers
SymbolCBX5
Alt. symbolsHP1-alpha
Entrez23468
HUGO1555
OMIM604478
RefSeqNM_012117
UniProtP45973
Other data
LocusChr. 12 q13.13
chromobox homolog 1
Identifiers
SymbolCBX1
Alt. symbolsHP1-beta
Entrez10951
HUGO1551
OMIM604511
RefSeqNM_006807
UniProtP83916
Other data
LocusChr. 17 q21.32
chromobox homolog 3
Identifiers
SymbolCBX3
Alt. symbolsHP1-gamma
Entrez11335
HUGO1553
OMIM604477
RefSeqNM_007276
UniProtQ13185
Other data
LocusChr. 7 p21-15

The family of heterochromatin protein 1 (HP1) ("Chromobox Homolog", CBX) consists of highly conserved proteins, which have important functions in the cell nucleus. These functions include gene repression by heterochromatin formation, transcriptional activation, regulation of binding of cohesion complexes to centromeres, sequesteration of genes to nuclear periphery, transcriptional arrest, maintenance of heterochromatin integrity, gene repression at the single nucleosome level and gene repression by heterochromatization of euchromatin. HP1 proteins are fundamental units of heterochromatin packaging that are enriched at the centromeres and telomeres of nearly all Eukaryotic chromosomes with the notable exception of budding yeast, in which a yeast-specific silencing complex of SIR (silent information regulatory) proteins serve a similar function. Members of the HP1 family are characterized by an N-terminal chromodomain and a C-terminal chromoshadow domain, separated by a Hinge region. HP1 is also found at euchromatic sites, where its binding correlates with gene repression. HP1 was originally discovered by Tharappel C James and Sarah Elgin in 1986 as a factor in the phenomenon known as position effect variegation in Drosophila melanogaster.[1][2]

Paralogs and orthologs

Three different paralogs of HP1 are found in Drosophila melanogaster, HP1a, HP1b and HP1c. Subsequently orthologs of HP1 were also discovered in S. pombe (Swi6), Xenopus (Xhp1α and Xhp1γ) and Chicken (CHCB1, CHCB2 and CHCB3). In mammals,[3] there are three paralogs: HP1α, HP1β and HP1γ. In Arabidopsis thaliana (a plant), there is one homolog: LIKE HETEROCHROMATIN PROTEIN 1 (LHP1), also known as TERMINAL FLOWER 2 (TFL2).[4]

HP1β in mammals

Main article: CBX1

HP1β interacts with the histone methyltransferase (HMTase) Suv(3-9)h1 and is a component of both pericentric and telomeric heterochromatin.[5][6][7] HP1β is a dosage-dependent modifier of pericentric heterochromatin-induced silencing[8] and silencing is thought to involve a dynamic association of the HP1β chromodomain with the tri-methylated Histone H3 Me(3)K9H3.

Interacting proteins

HP1 seems to interact with numerous other proteins/molecules with different cellular functions in different organisms. Some of these HP1 interacting partners are: histone H1, histone H3, methylated K9 histone H3, histone H4, histone methyltransferase, DNA methyltransferase, methyl CpG binding protein MeCP2, and the origin recognition complex protein ORC2

Binding affinity and cooperativity

HP1 binding affinity to nucleosomes containing histone H3 methylated at lysine K9 is higher than to those with unmethylated lysine K9. HP1 binds nucleosomes as a dimer and in principle can form multimeric complexes. Some studies have interpreted HP1 binding in terms of nearest-neighbor cooperative binding. This mode of chromatin interactions could potentially lead to spreading of HP1 along the nucleosome chain. However, the analysis of available data on HP1 binding to nucleosomal arrays in vitro shows that experimental HP1 binding isotherms can be explained by a simple model without cooperative interactions between neighboring HP1 dimers.[9]

See also

References

  1. ↑ James, T.C.; S.C Elgin (1986). "Identification of a nonhistone chromosomal protein associated with heterochromatin in Drosophila melanogaster and its gene". Mol. Cell. Biol. 6 (11): 3862–3872. PMC 367149. PMID 3099166.
  2. ↑ Eissenberg, J.C., James, T.C., Foster-Hartnett, D.M., Hartnett, T., Ngan, V.K.W., Craig, C., Elgin, S.C.R. (1990). "Mutation in a heterochromatin-specific chromosomal protein is associated with suppression of position-effect variegation in Drosophila melanogaster". Proceedings of the National Academy of Sciences of the United States of America. 87 (24): 9923–7. doi:10.1073/pnas.87.24.9923. PMC 55286. PMID 2124708.
  3. ↑ Singh PB; Miller JR; Pearce J; Kothary R; Burton RD; Paro R; James TC; Gaunt SJ. (February 1991). "A sequence motif found in a Drosophila heterochromatin protein is conserved in animals and plants". Nucleic Acids Res. 19 (4): 789–94. doi:10.1093/nar/19.4.789. PMC 333712. PMID 1708124.
  4. ↑ Kotake, Toshihisa; Takada, Shinobu; Nakahigashi, Kenji; Ohto, Masaaki; Goto, Koji (2003-06-15). "Arabidopsis TERMINAL FLOWER 2 Gene Encodes a Heterochromatin Protein 1 Homolog and Represses both FLOWERING LOCUS T to Regulate Flowering Time and Several Floral Homeotic Genes". Plant and Cell Physiology. 44 (6): 555–564. doi:10.1093/pcp/pcg091. ISSN 0032-0781. PMID 12826620.
  5. ↑ Aagaard L, Laible G, Selenko P, Schmid M, Dorn R, Schotta G, Kuhfittig S, Wolf A, Lebersorger A, Singh PB, Reuter G, Jenuwein T (April 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 J. 18 (7): 1923–38. doi:10.1093/emboj/18.7.1923. PMC 1171278. PMID 10202156.
  6. ↑ Wreggett KA, Hill F, James PS, Hutchings A, Butcher GW, Singh PB (1994). "A mammalian homologue of Drosophila heterochromatin protein 1 (HP1) is a component of constitutive heterochromatin". Cytogenet. Cell Genet. 66 (2): 99–103. doi:10.1159/000133676. PMID 8287692.
  7. ↑ Sharma GG; Hwang KK; Pandita RK; Gupta A; Dhar S; Parenteau J; Agarwal M; Worman HJ; Wellinger RJ; Pandita TK. (Nov 2003). "Human Heterochromatin Protein 1 Isoforms HP1Hsα and HP1Hsβ Interfere with hTERT-Telomere Interactions and Correlate with Changes in Cell Growth and Response to Ionizing Radiation". Mol. Cell. Biol. 23 (22): 8363–76. doi:10.1128/MCB.23.22.8363-8376.2003. PMC 262350. PMID 14585993.
  8. ↑ Festenstein R, Sharghi-Namini S, Fox M, Roderick K, Tolaini M, Norton T, Saveliev A, Kioussis D, Singh P (December 1999). "Heterochromatin protein 1 modifies mammalian PEV in a dose- and chromosomal-context-dependent manner". Nat. Genet. 23 (4): 457–61. doi:10.1038/70579. PMID 10581035.
  9. ↑ Teif V.B.; Kepper N.; Yserentant K; Wedemann G.; Rippe K. "Affinity, stoichiometry and cooperativity of heterochromatin protein 1 (HP1) binding to nucleosomal arrays". J. Phys.: Condens. Matter. arXiv:1408.6184.

Further reading

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