EN1_(gene) Knowpia

EN1
Identifiers
Aliases	EN1, engrailed homeobox 1, ENDOVESLB
External IDs	OMIM: 131290 MGI: 95389 HomoloGene: 50663 GeneCards: EN1
Gene location (Human)
Chr.	Chromosome 2 (human)
End	118,847,648 bp
Gene location (Mouse)
Chr.	Chromosome 1 (mouse)
End	120,535,721 bp
RNA expression pattern
	Top expressed in
	gastrocnemius muscle; ; skin of abdomen; ; biceps brachii; ; quadriceps femoris muscle; ; vastus lateralis muscle; ; skeletal muscle tissue; ; subcutaneous adipose tissue; ; deltoid muscle; ; lymph node; ; tibialis anterior muscle;
	Top expressed in
	sclerotome; ; surface ectoderm; ; rhombic lip; ; ventral tegmental area; ; pharynx; ; interpeduncular nucleus; ; substantia nigra; ; calvaria; ; inferior colliculus; ; footplate;
	More reference expression data
	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
	2019
	13798
	ENSG00000163064
	ENSMUSG00000058665
	Q05925
	P09065
	NM_001426
	NM_010133
	NP_001417
	NP_034263
	Wikidata
View/Edit Human	View/Edit Mouse

Homeobox protein engrailed-1 is a protein that in humans is encoded by the EN1 gene.^[5]^[6]

Function edit

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.^[6]

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.^[7] 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.^[8]

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,^[9] 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 edit

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000163064 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000058665 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ 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.
^ ^a ^b "Entrez Gene: EN1 engrailed homeobox 1".
^ 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.
^ 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.
^ 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.