Double negative epigenetics regulation of genes in differentiation of human endothelial stem cells into endothelium

Cover Page

Cite item

Abstract

Тhere are a number of genes which expression is characteristic for endothelium. Тranscription factors GAТA-2 and -3, endothelial NO synthitase (eNOS) are among them. During early embryogenesis epigenetics mechanisms of gene regulation plays an important role. Human embryonic stem cells (hESCs) represent a valuable model to study early embryogenesis events. Using the previously developed model of hESCs differentiation to functional endothelium we compared status of GAТA-2, GAТA-3 and eNOS gene's promoters methylation in hESCs, hESCs-derived purified endothelial cells and human umbilical vein endothelial cells (HUVEC). Hypermethylation of promoter regions of genes studied in hESCs correlates with gene silencing whereas hypomethylation in hESCs-derived endothelial cells and HUVECs correlated with the high level of expression. Overall our data indicate the importance of epigenetic regulation for tissue-specific differentiation and provide the evidence that in the course of in vitro differentiation ESCs undergo the same epigenetic program as differentiating cells of embryo in vivo.

Full Text

Restricted Access

About the authors

P. Yu. Volchkov

Vavilov Institute of General Genetics, RAS; Institute of Gene Biology, RAS

Author for correspondence.
Email: redaktor@celltranspl.ru
Russian Federation, Moscow; Moscow

M. A. Lagarkova

Vavilov Institute of General Genetics, RAS

Email: redaktor@celltranspl.ru
Russian Federation, Moscow

M. A. Рrokhorovich

Institute of Genetics and Cytology, Siberian branch of RAS

Email: redaktor@celltranspl.ru
Russian Federation, Novosibirsk

S. L. Kiselyev

Vavilov Institute of General Genetics, RAS

Email: redaktor@celltranspl.ru
Russian Federation, Moscow

References

  1. Zambidis E.T., Oberlin E., Tavian M. et al. Blood-forming endothelium in human ontogeny: lessons from in utero development and embryonic stem cell culture. Trends Cardiovasc. Med. 2006; 16(3): 95-101.
  2. Villar I.C., Francis S., Webb A. et al. Novel aspects of endothelium-dependent regulation of vascular tone. Kidney Int. 2006; 70(5): 840-53.
  3. Umetani M., Mataki C., Minegishi N. et al. Function of GATA transcription factors in induction of endothelial vascular cell adhesion molecule-1 by tumor necrosis factor-alpha. Arterioscler. Thromb. Vasc. Biol. 2001; 21(6): 917-22.
  4. Weiss M.J., Orkin S.H. GATA transcription factors: key regulators of hematopoiesis. Exp. Hematol. 1995; 23(2): 99-107.
  5. Minami T., Abid M.R., Zhang J. et al. Thrombin stimulation of vascular adhesion molecule-1 in endothelial cells is mediated by protein kinase C (PKC)-delta-NF-kappa B and PKC-zeta-GATA signaling pathways. J. Biol. Chem. 2003; 278(9): 6976-84.
  6. Tsai F.Y., Orkin S.H. Transcription factor GATA-2 is required for proliferation/survival of early hematopoietic cells and mast cell formation., but not for erythroid and myeloid terminal differentiation. Blood 1997; 89(10): 3636-43.
  7. Zhang R., Min W., Sessa W.C. Functional analysis of the human endothelial nitric oxide synthase promoter. Sp1 and GATA factors are necessary for basal transcription in endothelial cells. J. Biol. Chem. 1995; 270(25): 15320-6.
  8. George K.M., Leonard M.W., Roth M.E., et al. Embryonic expression and cloning of the murine GATA-3 gene. Development 1994; 120(9): 2673-86.
  9. Pan X., Minegishi N., Harigae H. et al. Identification of human GATA-2 gene distal IS exon and its expression in hematopoietic stem cell fractions. J. Biochem. 2000; 127(1): 105-12.
  10. Burch J.B. Regulation of GATA gene expression during vertebrate development. Semin. Cell Dev. Biol. 2005; 16(1): 71-81.
  11. Levenberg S., Golub J.S., Amit M. et al. Endothelial cells derived from human embryonic stem cells. Proc. Natl. Acad. Sci. USA 2002; 99(7): 4391-6.
  12. Grass J.A., Boyer M.E., Pal S. et al. GATA-1-dependent transcriptional repression of GATA-2 via disruption of positive autoregulation and domain-wide chromatin remodeling. Proc. Natl. Acad. Sci. USA 2003; 100(15): 8811-6.
  13. Pata I., Studer M., van Doorninck J.H. et al. The transcription factor GATA3 is a downstream effector of Hoxb1 specification in rhombomere 4. Development 1999; 126(23): 5523-31.
  14. Fish J.E., Marsden P.A. Endothelial nitric oxide synthase: insight into cell-specific gene regulation in the vascular endothelium. Cell Mol. Life Sci. 2006; 63(2): 144-62.
  15. Chan Y., Fish J.E., D'Abreo C. et al. The cell-specific expression of endothelial nitric-oxide synthase: a role for DNA methylation. J. Biol. Chem. 2004; 279(33): 35087-100.
  16. Lagarkova M.A., Volchkov P.Y., Lyakisheva A.V. et al. Diverse epigenetic profile of novel human embryonic stem cell lines. Cell Cycle. 2006; 5(4): 416-20.
  17. Bird A. DNA methylation patterns and epigenetic memory. Genes Dev. 2002;16(1): 6-21.
  18. Lugus J.J., Chung Y.S., Mills J.C. et al. GATA2 functions at multiple steps in hemangioblast development and differentiation. Development 2007; 134(2): 393-405.
  19. Asnagli H., Afkarian M., Murphy K.M. Cutting edge: Identification of an alternative GATA-3 promoter directing tissue-specific gene expression in mouse and human. J. Immunol. 2002; 168(9): 4268-71.
  20. Guillot P.V., Liu L., Kuivenhoven J.A., et al. Targeting of human eNOS promoter to the Hprt locus of mice leads to tissue-restricted transgene expression. Physiol. Genomics. 2000; 2(2): 77-83.
  21. Fish J.E., Matouk C.C., Rachlis A. et al. The expression of endothelial nitric- oxide synthase is controlled by a cell-specific histone code. J. Biol. Chem. 2005; 280(26): 24824-38.
  22. Zhao C., Meng A. Sp1-like transcription factors are regulators of embryonic development in vertebrates. Dev. Growth Differ. 2005; 47(4): 201-11.
  23. Xu D., Wilson T.J., Chan D. et al. Ets1 is required for p53 transcriptional activity in UV-induced apoptosis in embryonic stem cells. EMBO J. 2002; 21(15): 4081-93.
  24. Zvetkova I., Apedaile A., Ramsahoye B. et al. Global hypomethylation of the genome in XX embryonic stem cells. Nat. Genet. 2005; 37(11): 1274-9.

Supplementary files

Supplementary Files
Action
1. Fig. 1

Download (49KB)
2. Fig. 2

Download (90KB)
3. Fig. 3

Download (94KB)
4. Fig. 4

Download (96KB)
5. Fig. 5

Download (72KB)

Copyright (c) 2023 PJSC Human Stem Cells Institute



СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: ПИ № ФС 77 - 57156 от 11.03.2014.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies