Misplaced Pages

EN1
Identifiers
Aliases	EN1, engrailed homeobox 1, ENDOVESLB
External IDs	OMIM: 131290; MGI: 95389; HomoloGene: 50663; GeneCards: EN1; OMA:EN1 - orthologs
Gene location (Human) Chr. Chromosome 2 (human) Band 2q14.2 Start 118,842,171 bp End 118,847,648 bp
Gene location (Mouse) Chr. Chromosome 1 (mouse) Band 1 E2.3|1 52.74 cM Start 120,530,147 bp End 120,535,721 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in pars reticulata skin of leg gastrocnemius muscle muscle of thigh pars compacta skin of abdomen skin of hip skin of thigh skin of arm muscle of arm Top expressed in sclerotome Apical ectodermal ridge surface ectoderm rhombic lip thoracic vertebral column hair ventral tegmental area lumbar subsegment of spinal cord pharynx interpeduncular nucleus More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA binding sequence-specific DNA binding RNA polymerase II cis-regulatory region sequence-specific DNA binding DNA-binding transcription repressor activity, RNA polymerase II-specific DNA-binding transcription factor activity, RNA polymerase II-specific Cellular component nucleus RSC-type complex Biological process negative regulation of neuron apoptotic process skeletal system development dopaminergic neuron differentiation proximal/distal pattern formation regulation of transcription, DNA-templated multicellular organism growth adult locomotory behavior anatomical structure morphogenesis hindbrain development neuron development negative regulation of transcription by RNA polymerase II cerebellum development limb development multicellular organism development motor learning midbrain-hindbrain boundary development embryonic brain development drinking behavior embryonic limb morphogenesis neuron differentiation regulation of gene expression social behavior pigmentation dorsal/ventral pattern formation embryonic forelimb morphogenesis midbrain development positive regulation of transcription by RNA polymerase II negative regulation of neuron death regulation of transcription by RNA polymerase II Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 2019 13798 Ensembl ENSG00000163064 ENSMUSG00000058665 UniProt Q05925 P09065 RefSeq (mRNA) NM_001426 NM_010133 RefSeq (protein) NP_001417 NP_034263 Location (UCSC) Chr 2: 118.84 – 118.85 Mb Chr 1: 120.53 – 120.54 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

Homeobox protein engrailed-1 is a protein that in humans is encoded by the EN1 gene.

Function

Homeobox-containing genes are thought to have a role in controlling development. In Drosophila, the engrailed (en) gene plays an important role during development in segmentation, where it is required for the formation of posterior compartments. Different mutations in the mouse homologs, En1 and En2, produced different developmental defects that frequently are lethal. The human engrailed homologs 1 and 2 encode homeodomain-containing proteins and have been implicated in the control of pattern formation during development of the central nervous system and the limbs.

Engrailed (En) 1 is a homeobox gene that helps regulate development in the dorsal midbrain and anterior hindbrain (cerebellum and colliculi) of humans. It is also essential in regulating the establishment of a dorso-ventral pattern in developing limbs. The expression of En1 is regulated until 13 days after fertilization by Fgf8, which controls the development of the forebrain and hindbrain. En1 is first expressed in this region on day 9.5 after fertilization for about 12 hours until En2 is expressed. After En2 expression, En1 is expressed again in other tissues such as somites and limb ectoderm throughout development. A knockout mouse model with the En1 homeobox deleted was developed; mice died less than 24 hours after birth because appeared to be unable to feed. The brains of the mice were studied and most of the cerebellum, colliculi, and cranial nerves 3 and 4 were missing. There was clear deletion in the mid-hindbrain, isthmus, junction region that began at day 9.5 after fertilization. All of the mice demonstrated marked forepaw deformities including fusion of digits and abnormal dorso-ventral patterning. The 13th ribs and sternums displayed delayed and abnormal ossification. The mouse model demonstrated that the expression of En1 is critical in the correct development of the brain, limbs, and sternum.

In 2021, a group of scientists and physicians around Andrea Superti-Furga in Lausanne and Stefan Mundlos in Berlin showed that biallelic loss-of-function variants at the EN1 locus result in a human phenotype that includes a severe impairment of limb development as well as cerebellar aplasia, reproducing the phenotype first observed in the gene knock-out mice described above. They also found that there is a long non-coding RNA (lncRNA) element at approx. 300 kb distance from EN1, that they called MAENLI (for Master on Engrailed-1 in the Limbs), that is responsible for activation of EN1 gene expression in the developing limbs. The biallelic loss of the MAENLI lncRNA element results in impairment of limb development in humans as seen in the EN1-associated condition, while cerebellar development is not affected.

References

1. ^ GRCh38: Ensembl release 89: ENSG00000163064 – Ensembl, May 2017
2. ^ GRCm38: Ensembl release 89: ENSMUSG00000058665 – 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. Kohler A, Logan C, Joyner AL, Muenke M (Mar 1993). "Regional assignment of the human homeobox-containing gene EN1 to chromosome 2q13-q21". Genomics. 15 (1): 233–235. doi:10.1006/geno.1993.1045. PMID 8094370.
6. ^ "Entrez Gene: EN1 engrailed homeobox 1".
7. Sgaier SK, Lao Z, Villanueva MP, Berenshteyn F, Stephen D, Turnbull RK, Joyner AL (June 2007). "Genetic subdivision of the tectum and cerebellum into functionally related regions based on differential sensitivity to engrailed proteins". Development. 134 (12): 2325–35. doi:10.1242/dev.000620. PMC 2840613. PMID 17537797.
8. Wurst W, Auerbach AB, Joyner AL (July 1994). "Multiple developmental defects in Engrailed-1 mutant mice: an early mid-hindbrain deletion and patterning defects in forelimbs and sternum". Development. 120 (7): 2065–75. doi:10.1242/dev.120.7.2065. PMID 7925010.
9. Allou L, Balzano S, Magg A, Quinodoz M, Royer-Bertrand B, Schöpflin R, et al. (April 2021). "Non-coding deletions identify Maenli lncRNA as a limb-specific En1 regulator". Nature. 592 (7852): 93–98. Bibcode:2021Natur.592...93A. doi:10.1038/s41586-021-03208-9. hdl:21.11116/0000-0008-1272-3. PMID 33568816. S2CID 231882012.

Further reading

• Logan C, Hanks MC, Noble-Topham S, Nallainathan D, Provart NJ, Joyner AL (1993). "Cloning and sequence comparison of the mouse, human, and chicken engrailed genes reveal potential functional domains and regulatory regions". Developmental Genetics. 13 (5): 345–58. doi:10.1002/dvg.1020130505. PMID 1363401.
• Logan C, Willard HF, Rommens JM, Joyner AL (February 1989). "Chromosomal localization of the human homeo box-containing genes, EN1 and EN2". Genomics. 4 (2): 206–9. doi:10.1016/0888-7543(89)90301-7. PMID 2567700.
• Kozmik Z, Sure U, Rüedi D, Busslinger M, Aguzzi A (June 1995). "Deregulated expression of PAX5 in medulloblastoma". Proceedings of the National Academy of Sciences of the United States of America. 92 (12): 5709–13. Bibcode:1995PNAS...92.5709K. doi:10.1073/pnas.92.12.5709. PMC 41766. PMID 7777574.
• Loomis CA, Harris E, Michaud J, Wurst W, Hanks M, Joyner AL (July 1996). "The mouse Engrailed-1 gene and ventral limb patterning". Nature. 382 (6589): 360–3. Bibcode:1996Natur.382..360L. doi:10.1038/382360a0. PMID 8684466. S2CID 4326299.
• Joliot A, Trembleau A, Raposo G, Calvet S, Volovitch M, Prochiantz A (May 1997). "Association of Engrailed homeoproteins with vesicles presenting caveolae-like properties". Development. 124 (10): 1865–75. doi:10.1242/dev.124.10.1865. PMID 9169834.
• Mikkola I, Bruun JA, Holm T, Johansen T (February 2001). "Superactivation of Pax6-mediated transactivation from paired domain-binding sites by dna-independent recruitment of different homeodomain proteins". The Journal of Biological Chemistry. 276 (6): 4109–18. doi:10.1074/jbc.M008882200. PMID 11069920.
• Hartley JL, Temple GF, Brasch MA (November 2000). "DNA cloning using in vitro site-specific recombination". Genome Research. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863.
• Schaefer LK, Wang S, Schaefer TS (November 2001). "Functional interaction of Jun and homeodomain proteins". The Journal of Biological Chemistry. 276 (46): 43074–82. doi:10.1074/jbc.M102552200. PMID 11551904.
• Hori Y, Gu X, Xie X, Kim SK (April 2005). "Differentiation of insulin-producing cells from human neural progenitor cells". PLOS Medicine. 2 (4): e103. doi:10.1371/journal.pmed.0020103. PMC 1087208. PMID 15839736.
• Bachar-Dahan L, Goltzmann J, Yaniv A, Gazit A (June 2006). "Engrailed-1 negatively regulates beta-catenin transcriptional activity by destabilizing beta-catenin via a glycogen synthase kinase-3beta-independent pathway". Molecular Biology of the Cell. 17 (6): 2572–80. doi:10.1091/mbc.E06-01-0052. PMC 1474795. PMID 16571670.
• Atit R, Sgaier SK, Mohamed OA, Taketo MM, Dufort D, Joyner AL, et al. (August 2006). "Beta-catenin activation is necessary and sufficient to specify the dorsal dermal fate in the mouse". Developmental Biology. 296 (1): 164–76. doi:10.1016/j.ydbio.2006.04.449. PMID 16730693.

External links

• EN1+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

This article on a gene on human chromosome 2 is a stub. You can help Misplaced Pages by expanding it.

• v
• t
• e

• Genes on human chromosome 2
• Transcription factors
• Human chromosome 2 gene stubs