MEOX1

Mesodermal transcription factor that plays a key role in somitogenesis and is specifically required for sclerotome development.

Required for maintenance of the sclerotome polarity and formation of the cranio-cervical joints (PubMed:23290072, PubMed:24073994).

[1] - The formation of skeletal muscle: from somite to limb

Action

http://www.uniprot.org/uniprot/P50221#function

Binds specifically to the promoter of target genes and regulates their expression.

Activates expression of NKX3-2 in the sclerotome.

Activates expression of CDKN1A and CDKN2A in endothelial cells, acting as a regulator of vascular cell proliferation.

While it activates CDKN1A in a DNA-dependent manner, it activates CDKN2A in a DNA-independent manner.

Required for hematopoietic stem cell (HSCs) induction via its role in somitogenesis: specification of HSCs occurs via the deployment of a specific endothelial precursor population, which arises within a sub-compartment of the somite named endotome.

Analysis of pre-myogenic factors showed that expression of PAX3, MEOX1 and EYA2 was significantly increased by MYOD [2].

Meox1 promotes vascular smooth muscle cells (SMCs) phenotypic modulation and injury-induced vascular remodeling by regulating the FAK-ERK1/2-autophagy signaling cascade[3].

Meox1 initiates G2 cell-cycle arrest within muscle stem cells[4].

Pax3 is both necessary and sufficient to induce skeletal myogenesis, Meox1 is required for Pax3 expression and subsequent myogenic differentiation ([21–23] in [5]).

Transduction of hAFS (human amniotic fluid stem) cells with MYOD lentiviruses induces skeletal myogenic differentiation in vitro and morphological and functional regeneration of injured muscle in vivo. Analysis of pre-myogenic factors showed that expression of PAX3, MEOX1 and EYA2 was significantly increased by MYOD [6].

Pathways

ERK1/2 for vascular smooth muscle cells (SMCs) [3].

Diseases

Diseases associated with MEOX1 include Klippel-Feil Syndrome 2 and Isolated Klippel-Feil Syndrome.

References

1. Buckingham M, Bajard L, Chang T, Daubas P, Hadchouel J, Meilhac S, Montarras D, Rocancourt D, and Relaix F. The formation of skeletal muscle: from somite to limb. J Anat. 2003 Jan;202(1):59-68. DOI:10.1046/j.1469-7580.2003.00139.x |
2. Kim JA, Shon YH, Lim JO, Yoo JJ, Shin HI, and Park EK. MYOD mediates skeletal myogenic differentiation of human amniotic fluid stem cells and regeneration of muscle injury. Stem Cell Res Ther. 2013;4(6):147. DOI:10.1186/scrt358 |
3. Wu B, Zhang L, Zhu YH, Zhang YE, Zheng F, Yang JY, Guo LY, Li XY, Wang L, Tang JM, Chen SY, and Wang JN. Mesoderm/mesenchyme homeobox gene l promotes vascular smooth muscle cell phenotypic modulation and vascular remodeling. Int J Cardiol. 2018 Jan 15;251:82-89. DOI:10.1016/j.ijcard.2017.10.098 |
4. Nguyen PD, Gurevich DB, Sonntag C, Hersey L, Alaei S, Nim HT, Siegel A, Hall TE, Rossello FJ, Boyd SE, Polo JM, and Currie PD. Muscle Stem Cells Undergo Extensive Clonal Drift during Tissue Growth via Meox1-Mediated Induction of G2 Cell-Cycle Arrest. Cell Stem Cell. 2017 Jul 6;21(1):107-119.e6. DOI:10.1016/j.stem.2017.06.003 |
5. Dixon K, Chen J, and Li Q. Gene expression profiling discerns molecular pathways elicited by ligand signaling to enhance the specification of embryonic stem cells into skeletal muscle lineage. Cell Biosci. 2017;7:23. DOI:10.1186/s13578-017-0150-x |
6. Kim JA, Shon YH, Lim JO, Yoo JJ, Shin HI, and Park EK. MYOD mediates skeletal myogenic differentiation of human amniotic fluid stem cells and regeneration of muscle injury. Stem Cell Res Ther. 2013;4(6):147. DOI:10.1186/scrt358 |

Expression

Upregulated - mainly after 1 hour after exercise and has increased level after long training.

Coregulation

VASP (0.89), CDC42EP1 (0.88), IQCJ-SCHIP1 (0.87), TES(0.87), ABRACL(0.87), KCNK6(0.87), TINAGL1(0.87), GLIS2(0.86), PCGF2(0.86), IL27RA(0.86), VWA1(0.86), PLEKHG2(0.85), PDGFB(0.85), ENG(0.85), ERF(0.85), SHROOM1(0.84), FAM57A(0.84), ELFN1(0.84), PPP1R13L(0.84), ITGA5(0.84), RAB32(0.84), MYADM(0.84), RNF152(0.83), CNN2(0.83), CDR2L(0.83), TMC6(0.83), ZBTB46(0.83), NOVA2(0.87), TGFB1I1(0.83), ELF4(0.83), PGM2(0.83), GBP1(0.83), PRKD2(0.83), NOL4L(0.82), SH2D3C(0.82), ZYX(0.82), TPM4(0.82), EPHA2(0.82), NECTIN2(0.82), SERPINH1(0.82), ACTN4(0.82), MMRN2(0.81), TAL1(0.82), SPATA2L(0.81), TRIM47(0.81), TGFB1(0.81), MYH9(0.81), LCP2(0.81), YWHAH(0.81), BCL6B(0.81), DLL1(0.80), TAGLN2(0.80), TBC1D9(0.80), SOX18(0.80), ID2(0.80), TAGLN2P1(0.80), MARCKSL1(0.80), MYL6P5(0.80), DLC1(0.79), ACTG1(0.79), HEYL(0.79), KCTD15(0.79), ...

HOXA10(-0.76), CLCN1(-0.71), KIF1C(-0.70), ZNF865(-0.68), RYR1(-0.67), ZC2HC1C(-0.67), NR1H2(-0.66), ...