HP1BP3

Heterochromatin protein 1, binding protein 3 is a protein that in humans is encoded by the HP1BP3 gene.[5] It has been identified as a novel subtype of the linker histone H1, involved in the structure of heterochromatin [6][7][8]

HP1BP3
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2RQP
Identifiers
Aliases	HP1BP3, HP1-BP74, HP1BP74, heterochromatin protein 1 binding protein 3
External IDs	OMIM: 616072 MGI: 109369 HomoloGene: 7774 GeneCards: HP1BP3
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1p36.12 Start 20,742,679 bp[1] End 20,787,323 bp[1]
Gene location (Mouse) Chr. Chromosome 4 (mouse)[2] Band 4|4 D3 Start 138,216,296 bp[2] End 138,244,683 bp[2]
Gene ontology Molecular function • DNA binding • nucleosome binding • GO:0001948 protein binding • chromatin binding Cellular component • nucleosome • cell nucleus • chromosome • nuclear speck Biological process • regulation of nucleus size • nucleosome assembly • heterochromatin organization • regulation of transcription, DNA-templated • regulation of cell proliferation • cellular response to hypoxia Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	50809	15441
Ensembl	ENSG00000127483	ENSMUSG00000028759
UniProt	Q5SSJ5	Q3TEA8
RefSeq (mRNA)	NM_016287 NM_001372052	NM_001122896 NM_001122897 NM_001285478 NM_001285479 NM_001285480 NM_001285481 NM_010470 NM_001356431 NM_001356432
RefSeq (protein)	NP_057371 NP_001358981 NP_001363716 NP_001363717 NP_001363718 NP_001363719 NP_001363720 NP_001363721 NP_001363722 NP_001363723 NP_001363724 NP_001363725 NP_001363726	NP_001116368 NP_001116369 NP_001272407 NP_001272408 NP_001272409 NP_001272410 NP_034600 NP_001343360 NP_001343361
Location (UCSC)	Chr 1: 20.74 – 20.79 Mb	Chr 4: 138.22 – 138.24 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Model organisms

Hp1bp3 knockout mouse phenotype

Characteristic	Phenotype
Homozygote viability	Abnormal
Recessive lethal study	Normal
Fertility	Normal
Body weight	Abnormal[9]
Anxiety	Normal
Neurological assessment	Normal
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Abnormal[10]
Radiography	Normal
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Abnormal[11]
Haematology	Normal
Peripheral blood lymphocytes	Abnormal
Micronucleus test	Normal
Heart weight	Abnormal[12]
Eye Histopathology	Normal
Citrobacter infection	Normal[13]
All tests and analysis from[14][15]

Model organisms have been used in the study of HP1BP3 function. A conditional knockout mouse line, called Hp1bp3^{tm1a(EUCOMM)Wtsi}[16][17] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists — at the Wellcome Trust Sanger Institute.[18][19][20] Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[14][21] Twenty three tests were carried out and six significant phenotypes were reported. Fewer homozygous mutant embryos were identified during gestation than predicted by Mendelian ratio. Homozygous mutant female adults had decreased body weight, heart weight and bone mineral density, and increased blood urea levels and T cell number.[14]

HP1BP3 deficiency in mice results in severe dwarfism and impaired bone mass, caused by altered endocrine IGF-1 signaling.[22] The gene is highly expressed in the brain and a number of behavioral phenotypes have been described for the mice. Lack of HP1BP3 led to impaired maternal behavior and reduced anxiety, leading to a dramatic reduction in litter survival.[23] This may be related to the connection between HP1BP3 and postpartum depression in humans.[24] Finally, HP1BP3 has been implicated in Alzheimer's disease..[25]

References

1. GRCh38: Ensembl release 89: ENSG00000127483 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000028759 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: heterochromatin protein 1, binding protein 3". Retrieved 2011-08-30.
6. Garfinkel BP, Melamed-Book N, Anuka E, Bustin M, Orly J (February 2015). "HP1BP3 is a novel histone H1 related protein with essential roles in viability and growth". Nucleic Acids Research. 43 (4): 2074–90. doi:10.1093/nar/gkv089. PMC 4344522. PMID 25662603.
7. Dutta B, Ren Y, Hao P, Sim KH, Cheow E, Adav S, Tam JP, Sze SK (September 2014). "Profiling of the Chromatin-associated Proteome Identifies HP1BP3 as a Novel Regulator of Cell Cycle Progression". Molecular & Cellular Proteomics. 13 (9): 2183–97. doi:10.1074/mcp.M113.034975. PMC 4159643. PMID 24830416.
8. Hayashihara K, Uchiyama S, Shimamoto S, Kobayashi S, Tomschik M, Wakamatsu H, No D, Sugahara H, Hori N, Noda M, Ohkubo T, Zlatanova J, Matsunaga S, Fukui K (February 2010). "The middle region of an HP1-binding protein, HP1-BP74, associates with linker DNA at the entry/exit site of nucleosomal DNA". The Journal of Biological Chemistry. 285 (9): 6498–507. doi:10.1074/jbc.M109.092833. PMC 2825445. PMID 20042602.
9. "Body weight data for Hp1bp3". Wellcome Trust Sanger Institute.
10. "DEXA data for Hp1bp3". Wellcome Trust Sanger Institute.
11. "Clinical chemistry data for Hp1bp3". Wellcome Trust Sanger Institute.
12. "Heart weight data for Hp1bp3". Wellcome Trust Sanger Institute.
13. "Citrobacter infection data for Hp1bp3". Wellcome Trust Sanger Institute.
14. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88 (S248). doi:10.1111/j.1755-3768.2010.4142.x.
15. Mouse Resources Portal, Wellcome Trust Sanger Institute.
16. "International Knockout Mouse Consortium".
17. "Mouse Genome Informatics".
18. Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (June 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
19. Dolgin E (June 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
20. Collins FS, Rossant J, Wurst W (January 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
21. van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.
22. Garfinkel BP, Arad S, Le PT, Bustin M, Rosen CJ, Gabet Y, Orly J (December 2015). "Proportionate Dwarfism in Mice Lacking Heterochromatin Protein 1 Binding Protein 3 (HP1BP3) Is Associated With Alterations in the Endocrine IGF-1 Pathway". Endocrinology. 156 (12): 4558–70. doi:10.1210/en.2015-1668. PMC 5393342. PMID 26402843.
23. Garfinkel BP, Arad S, Neuner S, Netser S, Wagner S, Kaczorowski CC, Rosen CJ, Gal M, Soreq H, Orly J (July 2016). "HP1BP3 expression determines maternal behavior and offspring survival". Genes, Brain, and Behavior. 15: 678–88. doi:10.1111/gbb.12312. PMID 27470444.
24. Guintivano J, Arad M, Gould TD, Payne JL, Kaminsky ZA (May 2014). "Antenatal prediction of postpartum depression with blood DNA methylation biomarkers". Molecular Psychiatry. 19 (5): 560–7. doi:10.1038/mp.2013.62. PMID 23689534.
25. Neuner SM, Garfinkel BP, Wilmott LA, Ignatowska-Jankowska BM, Citri A, Orly J, Lu L, Overall RW, Mulligan MK, Kempermann G, Williams RW, O'Connell KM, Kaczorowski CC (June 2016). "Systems genetics identifies Hp1bp3 as a novel modulator of cognitive aging". Neurobiology of Aging. 46: 58–67. doi:10.1016/j.neurobiolaging.2016.06.008. PMC 5018442. PMID 27460150.

Further reading

• Rose JE, Behm FM, Drgon T, Johnson C, Uhl GR. "Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score". Molecular Medicine. 16 (7–8): 247–53. doi:10.2119/molmed.2009.00159. PMC 2896464. PMID 20379614.
• Ouyang J, Shi Y, Valin A, Xuan Y, Gill G (April 2009). "Direct binding of CoREST1 to SUMO-2/3 contributes to gene-specific repression by the LSD1/CoREST1/HDAC complex". Molecular Cell. 34 (2): 145–54. doi:10.1016/j.molcel.2009.03.013. PMC 2727917. PMID 19394292.
• Martins-de-Souza D, Gattaz WF, Schmitt A, Rewerts C, Maccarrone G, Dias-Neto E, Turck CW (April 2009). "Prefrontal cortex shotgun proteome analysis reveals altered calcium homeostasis and immune system imbalance in schizophrenia". European Archives of Psychiatry and Clinical Neuroscience. 259 (3): 151–63. doi:10.1007/s00406-008-0847-2. PMID 19165527.
• Flachsbart F, Franke A, Kleindorp R, Caliebe A, Blanché H, Schreiber S, Nebel A (December 2010). "Investigation of genetic susceptibility factors for human longevity - a targeted nonsynonymous SNP study". Mutation Research. 694 (1–2): 13–9. doi:10.1016/j.mrfmmm.2010.08.006. PMID 20800603.
• Hayashihara K, Uchiyama S, Shimamoto S, Kobayashi S, Tomschik M, Wakamatsu H, No D, Sugahara H, Hori N, Noda M, Ohkubo T, Zlatanova J, Matsunaga S, Fukui K (February 2010). "The middle region of an HP1-binding protein, HP1-BP74, associates with linker DNA at the entry/exit site of nucleosomal DNA". The Journal of Biological Chemistry. 285 (9): 6498–507. doi:10.1074/jbc.M109.092833. PMC 2825445. PMID 20042602.
• Gautier VW, Gu L, O'Donoghue N, Pennington S, Sheehy N, Hall WW (2009). "In vitro nuclear interactome of the HIV-1 Tat protein". Retrovirology. 6: 47. doi:10.1186/1742-4690-6-47. PMC 2702331. PMID 19454010.