MESP1

MESP1
Identifikatori
Aliasi	MESP1
Vanjski ID-jevi	OMIM: 608689 MGI: 107785 HomoloGene: 32039 GeneCards: MESP1
Lokacija gena (čovjek)
Hrom.	Hromosom 15 (čovjek)
Kraj	89,751,249 bp
Lokacija gena (miš)
Hrom.	Hromosom 7 (miš)
Kraj	79,443,536 bp
Ontologija gena
Molekularna funkcija	• vezivanje sa DNK; • protein dimerization activity; • GO:0001131, GO:0001151, GO:0001130, GO:0001204 DNA-binding transcription factor activity; • GO:0000980 RNA polymerase II cis-regulatory region sequence-specific DNA binding; • GO:0001077, GO:0001212, GO:0001213, GO:0001211, GO:0001205 DNA-binding transcription activator activity, RNA polymerase II-specific; • GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific;
Ćelijska komponenta	• jedro;
Biološki proces	• Notch signaling pathway; • neurogenesis; • cardiac ventricle formation; • GO:0009373 regulation of transcription, DNA-templated; • lateral mesoderm development; • positive regulation of hepatocyte differentiation; • positive regulation of heart induction by negative regulation of canonical Wnt signaling pathway; • negative regulation of mesodermal cell fate specification; • cardiac muscle cell differentiation; • positive regulation of Notch signaling pathway involved in heart induction; • cardiac vascular smooth muscle cell differentiation; • signal transduction involved in regulation of gene expression; • heart morphogenesis; • transcription by RNA polymerase II; • transcription, DNA-templated; • sinus venosus morphogenesis; • heart looping; • GO:0060469, GO:0009371 positive regulation of transcription, DNA-templated; • cardioblast migration; • cardiac cell fate determination; • multicellular organism development; • Gastrulacija; • embryonic heart tube morphogenesis; • growth involved in heart morphogenesis; • positive regulation of striated muscle cell differentiation; • cardioblast migration to the midline involved in heart field formation; • endothelial cell differentiation; • sinoatrial node cell differentiation; • negative regulation of endodermal cell fate specification; • secondary heart field specification; • cardiac atrium formation; • GO:0045996 negative regulation of transcription, DNA-templated; • cardioblast anterior-lateral migration; • mesodermal cell migration; • positive regulation of Notch signaling pathway; • GO:0003257, GO:0010735, GO:1901228, GO:1900622, GO:1904488 positive regulation of transcription by RNA polymerase II; • mesoderm formation; • somitogenesis; • embryonic pattern specification;
	Izvori:Amigo / QuickGO
Ortolozi
	55897
	17292
	ENSG00000166823
	ENSMUSG00000030544
	Q9BRJ9
	P97309
	NM_018670
	NM_008588
	NP_061140
	NP_032614
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Mišji mezodermni stražnji homolog 1 je protein koji je kod ljudi kodiran genom MESP1.^[5] MESP1 je transkripcijski faktor koji regulira specifikaciju kardiovaskularnih progenitora.^[6]

Gen MESP1 kodira člana porodice heliks-petlja-heliks (bHLH), porodice transkripcijskih regulatornih proteina koji mogu imati ulogu u razvoju novonastajućeg mezoderma. Saga et al. (1996) mapirali su gen Mesp1 na mišji hromosom 7, unutar regije koja dijeli homologiju sintezije ljudskim hromosomom 15q26. Mišji Mesp1 i Mesp2 odvojeni su za otprilike 23 kb, pozicionirani su glava uz glavu i transkribirani iz interlokusne regije. Odredili su da gen Mesp1 ima dva egzona.^[7]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 268 aminokiselina, a molekulska težina 28.501 Da.^[8]

10	20	30	40	50
MAQPLCPPLS	ESWMLSAAWG	PTRRPPPSDK	DCGRSLVSSP	DSWGSTPADS
PVASPARPGT	LRDPRAPSVG	RRGARSSRLG	SGQRQSASER	EKLRMRTLAR
ALHELRRFLP	PSVAPAGQSL	TKIETLRLAI	RYIGHLSAVL	GLSEESLQRR
CRQRGDAGSP	RGCPLCPDDC	PAQMQTRTQA	EGQGQGRGLG	LVSAVRAGAS
WGSPPACPGA	RAAPEPRDPP	ALFAEAACPE	GQAMEPSPPS	PLLPGDVLAL
LETWMPLSPL	EWLPEEPK

Simboli

C: Cistein
D: Asparaginska kiselina
E: Glutaminska kiselina
F: Fenilalanin
G: Glicin
H: Histidin
I: Izoleucin
K: Lizin
L: Leucin
M: Metionin
N: Asparagin
P: Prolin
Q: Glutamin
R: Arginin
S: Serin
T: Treonin
V: Valin
W: Triptofan
Y: Tirozin

Kloniranje i ekspresija

Saga et al. (1996) identificirali su miš Mesp1 gen supstraktivnom hibridizacijom kako bi izolirali gene koji sudjeluju u diferencijaciji iskonskih staničnih ćelija miša. Transkript Mesp1 kodira pretpostavljeni faktor transkripcije od 243 aminokiseline koji sadrži motiv bHLH.^[9] Whittock et al. (2004) objavili da ljudski MESP1 i MESP2 imaju 47,4% aminokiselinskog identiteta. I MESP1 i MESP2 sadrže jedinstveni CPXCP motiv C-terminalno na bHLH domenu. N- i C-terminalni domeni MESP1 odvojeni su GQ regijom sa po dva ponavljanja, koja je u MESP2 proširena na 13 ponavljanja.

Funkcija gena

Hibridizacijom insitu mišjih embriona, Saga et al. (1996) otkrili su najraniju ekspresiju Mesp1 6,5 dana nakon koitusa (dpc) u svim novonastalim mezodermnim ćelijama. Na 7,5 dpc, ekspresija Mesp1 otkrivena je u dnu alantoisa. Ubrzo nakon toga, ekspresija se proširila na bočne rubove mezoderma repnih pupova, po obrascu koji odgovara onom početne migracije primordijalnih klica, prije nego što nestanu. Nije otkrivena ekspresija Mesp1 u kasnijem razvoju ili u tkivima odraslih, osim u sjemenicima, u kojima je uočena drugačija izoforma od one viđene u ranom mezodermu. Zaključili su da Mesp1 može i,ati važnu ulogu u razvoju novonastajućeg mezoderma, uključujući primordijalne zametne ćelije.

Lescroart et al. (2018) izveli su sekvenciranje jednolančane RNK divljih i Mesp1 nultih kardiovaskularnih prekursora (CP) kod miševa i pokazali da su populacije Mesp1 CP molekulaki različite i da obuhvataju kontinuum između epiblastnih i kasnijih mezodermnih ćelija, uključujući hematopoetske prekursore. Analiza jednolančanih transkriptoma CP s nedostatkom Mesp1 pokazala je da je Mesp1 potreban za izlazak iz pluripotentnog stanja i indukciju programa ekspresije kardiovaskularnih gena. Identificirali su različite skupine kardiovaskularnih prekursora Mesp1, koje odgovaraju rodovima predanim različitim ćelijama lozama i regijama srca, identificirajući molekulske značajke povezane s ranim ograničenjem loze i regionalnom segregacijom srca u ranoj fazi mišje gastrulacije.^[10]

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000166823 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000030544 - Ensembl, maj 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.
^ "Entrez Gene: Mesoderm posterior 1 homolog (mouse)".
^ Bondue A, Lapouge G, Paulissen C, Semeraro C, Iacovino M, Kyba M, Blanpain C (juli 2008). "Mesp1 acts as a master regulator of multipotent cardiovascular progenitor specification". Cell Stem Cell (jezik: engleski). 3 (1): 69–84. doi:10.1016/j.stem.2008.06.009. PMID 18593560.
^ Whittock, N. V., Sparrow, D. B., Wouters, M. A., Sillence, D., Ellard, S., Dunwoodie, S. L., Turnpenny, P. D. Mutated MESP2 causes spondylocostal dysostosis in humans. Am. J. Hum. Genet. 74: 1249-1254, 2004. PubMed: 15122512
^ "UniProt, Q9BRJ9". Pristupljeno 15. 7. 2021.
^ Saga, Y., Hata, N., Kobayashi, S., Magnuson, T., Seldin, M. F., Taketo, M. M. MesP1: a novel basic helix-loop-helix protein expressed in the nascent mesodermal cells during mouse gastrulation. Development 122: 2769-2778, 1996.
^ Lescroart, F., Wang, X., Lin, X., Swedlund, B., Gargouri, S., Sanchez-Danes, A., Moignard, V., Dubois, C., Paulissen, C., Kinston, S., Gottgens, B., Blanpain, C. Defining the earliest step of cardiovascular lineage segregation by single-cell RNA-seq. Science 359: 1177-181, 2018. PubMed: 29371425

Dopunska literatura

David R, Brenner C, Stieber J, Schwarz F, Brunner S, Vollmer M, Mentele E, Müller-Höcker J, Kitajima S, Lickert H, Rupp R, Franz WM (mart 2008). "MesP1 drives vertebrate cardiovascular differentiation through Dkk-1-mediated blockade of Wnt-signalling". Nature Cell Biology. 10 (3): 338–45. doi:10.1038/ncb1696. PMID 18297060.
Islas JF, Liu Y, Weng KC, Robertson MJ, Zhang S, Prejusa A, Harger J, Tikhomirova D, Chopra M, Iyer D, Mercola M, Oshima RG, Willerson JT, Potaman VN, Schwartz RJ (august 2012). "Transcription factors ETS2 and MESP1 transdifferentiate human dermal fibroblasts into cardiac progenitors". Proceedings of the National Academy of Sciences of the United States of America. 109 (32): 13016–21. doi:10.1073/pnas.1120299109. PMC 3420197. PMID 22826236.
Saga Y, Hata N, Kobayashi S, Magnuson T, Seldin MF, Taketo MM (septembar 1996). "MesP1: a novel basic helix-loop-helix protein expressed in the nascent mesodermal cells during mouse gastrulation". Development. 122 (9): 2769–78. PMID 8787751.
Haraguchi S, Kitajima S, Takagi A, Takeda H, Inoue T, Saga Y (oktobar 2001). "Transcriptional regulation of Mesp1 and Mesp2 genes: differential usage of enhancers during development". Mechanisms of Development. 108 (1–2): 59–69. doi:10.1016/S0925-4773(01)00478-6. PMID 11578861.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000166823 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000030544 - Ensembl, maj 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.

[entrez-5] "Entrez Gene: Mesoderm posterior 1 homolog (mouse)".

[6] Bondue A, Lapouge G, Paulissen C, Semeraro C, Iacovino M, Kyba M, Blanpain C (juli 2008). "Mesp1 acts as a master regulator of multipotent cardiovascular progenitor specification". Cell Stem Cell (jezik: engleski). 3 (1): 69–84. doi:10.1016/j.stem.2008.06.009. PMID 18593560.

[7] Whittock, N. V., Sparrow, D. B., Wouters, M. A., Sillence, D., Ellard, S., Dunwoodie, S. L., Turnpenny, P. D. Mutated MESP2 causes spondylocostal dysostosis in humans. Am. J. Hum. Genet. 74: 1249-1254, 2004. PubMed: 15122512

[UniProt-8] "UniProt, Q9BRJ9". Pristupljeno 15. 7. 2021.

[9] Saga, Y., Hata, N., Kobayashi, S., Magnuson, T., Seldin, M. F., Taketo, M. M. MesP1: a novel basic helix-loop-helix protein expressed in the nascent mesodermal cells during mouse gastrulation. Development 122: 2769-2778, 1996.

[10] Lescroart, F., Wang, X., Lin, X., Swedlund, B., Gargouri, S., Sanchez-Danes, A., Moignard, V., Dubois, C., Paulissen, C., Kinston, S., Gottgens, B., Blanpain, C. Defining the earliest step of cardiovascular lineage segregation by single-cell RNA-seq. Science 359: 1177-181, 2018. PubMed: 29371425

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