HIRA

This article is about the gene. For other uses, see Hira (disambiguation).

HIRA
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2I32
Identifiers
Aliases	HIRA , DGCR1, TUP1, TUPLE1, histone cell cycle regulator
External IDs	OMIM: 600237 MGI: 99430 HomoloGene: 48172 GeneCards: HIRA
Gene location (Human) Chr. Chromosome 22 (human) [1] Band 22q11.21 Start 19,330,698 bp [1] End 19,447,450 bp [1]
Gene location (Mouse) Chr. Chromosome 16 (mouse) [2] Band 16 A3|16 11.69 cM Start 18,695,787 bp [2] End 18,789,059 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in left lobe of thyroid gland right lobe of thyroid gland ganglionic eminence stromal cell of endometrium gastrocnemius muscle prefrontal cortex thymus amygdala dorsolateral prefrontal cortex human penis Top expressed in superior frontal gyrus yolk sac lip ganglionic eminence cerebellar cortex thymus morula duodenum esophagus primitive streak More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA-binding transcription factor activity protein binding transcription corepressor activity nucleosome binding DNA binding Cellular component PML body extracellular exosome nucleus nucleoplasm HIR complex chromosome, centromeric region protein-containing complex Biological process regulation of transcription by RNA polymerase II muscle cell differentiation anatomical structure morphogenesis regulation of transcription, DNA-templated gastrulation osteoblast differentiation transcription, DNA-templated negative regulation of nucleic acid-templated transcription chromatin organization mitotic sister chromatid segregation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 7290 15260 Ensembl ENSG00000100084 ENSMUSG00000022702 UniProt P54198 Q61666 RefSeq (mRNA) NM_003325 NM_001005228 NM_010435 RefSeq (protein) NP_003316 NP_034565 Location (UCSC) Chr 22: 19.33 – 19.45 Mb Chr 16: 18.7 – 18.79 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Protein HIRA is a protein that in humans is encoded by the HIRA gene. ^{[5] [6] [7] [8]} This gene is mapped to 22q11.21, centromeric to COMT. ^[8]

Function

The specific function of this protein has yet to be determined; however, it has been speculated to play a role in transcriptional regulation and/or chromatin and histone metabolism. ^[8]

Research done by Salomé Adam, Sophie E. Polo, and Geneviève Almouzni indicate that HIRA proteins are involved in restarting transcription after UVC damage. ^[9] Function of HIRA gene can be effectively examined by siRNA knockdown based on an independent validation. ^[10]

Clinical significance

It is considered the primary candidate gene in some haploinsufficiency syndromes such as DiGeorge syndrome, and insufficient production of the gene may disrupt normal embryonic development. ^[8]

Model organisms

Hira knockout mouse phenotype

Characteristic	Phenotype
Homozygote viability	Abnormal
Fertility	Normal
Body weight	Normal
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	Normal
Radiography	Normal
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Haematology	Abnormal [11]
Peripheral blood lymphocytes	Normal
Micronucleus test	Normal
Heart weight	Normal
Eye Histopathology	Normal
Salmonella infection	Normal [12]
All tests and analysis from [13] [14]

Model organisms have been used in the study of HIRA function. A conditional knockout mouse line, called Hira^{tm1a(EUCOMM)Wtsi [15] [16]} 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. ^{[17] [18] [19]}

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. ^{[13] [20]} Twenty two tests were carried out on mutant mice and two significant abnormalities were observed. ^[13] No homozygous mutant mice survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice and a decreased leukocyte cell number was recorded in male animals. ^[13]

Interactions

HIRA has been shown to interact with HIST1H2BK. ^[21]

References

1. GRCh38: Ensembl release 89: ENSG00000100084 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000022702 - 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. Halford S, Wadey R, Roberts C, Daw SC, Whiting JA, O'Donnell H, Dunham I, Bentley D, Lindsay E, Baldini A (Mar 1994). "Isolation of a putative transcriptional regulator from the region of 22q11 deleted in DiGeorge syndrome, Shprintzen syndrome and familial congenital heart disease". Hum Mol Genet. 2 (12): 2099–107. doi:10.1093/hmg/2.12.2099. PMID   8111380.
6. Lamour V, Lécluse Y, Desmaze C, Spector M, Bodescot M, Aurias A, Osley MA, Lipinski M (Sep 1995). "A human homolog of the S. cerevisiae HIR1 and HIR2 transcriptional repressors cloned from the DiGeorge syndrome critical region". Hum Mol Genet. 4 (5): 791–9. doi:10.1093/hmg/4.5.791. PMID   7633437.
7. Magnaghi P, Roberts C, Lorain S, Lipinski M, Scambler PJ (Oct 1998). "HIRA, a mammalian homologue of Saccharomyces cerevisiae transcriptional co-repressors, interacts with Pax3". Nat Genet. 20 (1): 74–7. doi: 10.1038/1739 . PMID   9731536. S2CID   19736941.
8. "Entrez Gene: HIRA HIR histone cell cycle regulation defective homolog A (S. cerevisiae)".
9. Adam, Salomé; Polo, Sophie E.; Almouzni, Geneviève (26 September 2013). "Transcription Recovery after DNA Damage Requires Chromatin Priming by the H3.3 Histone Chaperone HIRA". Cell. 155 (1): 94–106. doi: 10.1016/j.cell.2013.08.029 . PMID   24074863. S2CID   3147953.
10. Munkácsy, Gyöngyi; Sztupinszki, Zsófia; Herman, Péter; Bán, Bence; Pénzváltó, Zsófia; Szarvas, Nóra; Győrffy, Balázs (2016). "Validation of RNAi Silencing Efficiency Using Gene Array Data shows 18.5% Failure Rate across 429 Independent Experiments". Molecular Therapy: Nucleic Acids. 5 (9): e366. doi:10.1038/mtna.2016.66. PMC   5056990 . PMID   27673562.
11. "Haematology data for Hira". Wellcome Trust Sanger Institute.
12. "Salmonella infection data for Hira". Wellcome Trust Sanger Institute.
13. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x. S2CID   85911512.
14. Mouse Resources Portal, Wellcome Trust Sanger Institute.
15. "International Knockout Mouse Consortium".
16. "Mouse Genome Informatics".
17. 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 (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–342. doi:10.1038/nature10163. PMC   3572410 . PMID   21677750.
18. Dolgin E (2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID   21677718.
19. Collins FS, Rossant J, Wurst W (2007). "A Mouse for All Reasons". Cell. 128 (1): 9–13. doi: 10.1016/j.cell.2006.12.018 . PMID   17218247. S2CID   18872015.
20. van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biol. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC   3218837 . PMID   21722353.
21. Lorain S, Quivy JP, Monier-Gavelle F, Scamps C, Lécluse Y, Almouzni G, Lipinski M (September 1998). "Core histones and HIRIP3, a novel histone-binding protein, directly interact with WD repeat protein HIRA". Mol. Cell. Biol. 18 (9): 5546–56. doi:10.1128/MCB.18.9.5546. PMC   109139 . PMID   9710638.

Further reading

• Lorain S, Demczuk S, Lamour V, Toth S, Aurias A, Roe BA, Lipinski M (1996). "Structural Organization of the WD repeat protein-encoding gene HIRA in the DiGeorge syndrome critical region of human chromosome 22". Genome Res. 6 (1): 43–50. doi: 10.1101/gr.6.1.43 . PMID   8681138.
• Llevadot R, Scambler P, Estivill X, Pritchard M (1997). "Genomic organization of TUPLE1/HIRA: a gene implicated in DiGeorge syndrome". Mamm. Genome. 7 (12): 911–4. doi:10.1007/s003359900268. PMID   8995764. S2CID   35176001.
• Lorain S, Quivy JP, Monier-Gavelle F, Scamps C, Lécluse Y, Almouzni G, Lipinski M (1998). "Core histones and HIRIP3, a novel histone-binding protein, directly interact with WD repeat protein HIRA". Mol. Cell. Biol. 18 (9): 5546–56. doi:10.1128/MCB.18.9.5546. PMC   109139 . PMID   9710638.
• Hall C, Nelson DM, Ye X, Baker K, DeCaprio JA, Seeholzer S, Lipinski M, Adams PD (2001). "HIRA, the human homologue of yeast Hir1p and Hir2p, is a novel cyclin-cdk2 substrate whose expression blocks S-phase progression". Mol. Cell. Biol. 21 (5): 1854–65. doi:10.1128/MCB.21.5.1854-1865.2001. PMC   86753 . PMID   11238922.
• Lorain S, Lécluse Y, Scamps C, Mattéi MG, Lipinski M (2001). "Identification of human and mouse HIRA-interacting protein-5 (HIRIP5), two mammalian representatives in a family of phylogenetically conserved proteins with a role in the biogenesis of Fe/S proteins". Biochim. Biophys. Acta. 1517 (3): 376–83. doi:10.1016/S0167-4781(00)00300-6. PMID   11342215.
• Lehner B, Sanderson CM (2004). "A protein interaction framework for human mRNA degradation". Genome Res. 14 (7): 1315–23. doi:10.1101/gr.2122004. PMC   442147 . PMID   15231747.
• Collins JE, Wright CL, Edwards CA, Davis MP, Grinham JA, Cole CG, Goward ME, Aguado B, Mallya M, Mokrab Y, Huckle EJ, Beare DM, Dunham I (2005). "A genome annotation-driven approach to cloning the human ORFeome". Genome Biol. 5 (10): R84. doi:10.1186/gb-2004-5-10-r84. PMC   545604 . PMID   15461802.
• Gocke CB, Yu H, Kang J (2005). "Systematic identification and analysis of mammalian small ubiquitin-like modifier substrates". J. Biol. Chem. 280 (6): 5004–12. doi: 10.1074/jbc.M411718200 . PMID   15561718.
• Zhang R, Poustovoitov MV, Ye X, Santos HA, Chen W, Daganzo SM, Erzberger JP, Serebriiskii IG, Canutescu AA, Dunbrack RL, Pehrson JR, Berger JM, Kaufman PD, Adams PD (2005). "Formation of MacroH2A-containing senescence-associated heterochromatin foci and senescence driven by ASF1a and HIRA". Dev. Cell. 8 (1): 19–30. doi: 10.1016/j.devcel.2004.10.019 . PMID   15621527.
• Ahmad A, Kikuchi H, Takami Y, Nakayama T (2005). "Different roles of N-terminal and C-terminal halves of HIRA in transcription regulation of cell cycle-related genes that contribute to control of vertebrate cell growth". J. Biol. Chem. 280 (37): 32090–100. doi: 10.1074/jbc.M501426200 . PMID   16024922.
• Tang Y, Poustovoitov MV, Zhao K, Garfinkel M, Canutescu A, Dunbrack R, Adams PD, Marmorstein R (2006). "Structure of a human ASF1a-HIRA complex and insights into specificity of histone chaperone complex assembly". Nat. Struct. Mol. Biol. 13 (10): 921–9. doi:10.1038/nsmb1147. PMC   2933817 . PMID   16980972.
• Zhang R, Chen W, Adams PD (2007). "Molecular dissection of formation of senescence-associated heterochromatin foci". Mol. Cell. Biol. 27 (6): 2343–58. doi:10.1128/MCB.02019-06. PMC   1820509 . PMID   17242207.