User:Professor L123/KDM1A

KDM1A

KDM1A (also referred to as LSD1/AOF2/BHC110) can act on mono- and dimethylated H3K4 and H3K9. This enzyme can have roles critical in embryogenesis and tissue-specific differentiation, as well as oocyte growth.[1] KDM1A was the first demethylase to be discovered and thus it has been studied most extensively.[2]

Deletion of the gene for KDM1A can have effects on the growth and differentiation of embryonic stem cells and can lead to embryonic lethality in knockout mice, who do not produce the KDM1A gene product.[3][4] KDM1A is also thought to play a role in cancer, as poorer outcomes can be correlated with higher expression of this gene.[5][6] Therefore, the inhibition of KDM1A may be a possible treatment for cancer.[7][8] KDM1A has many different binding partners, which may be necessary for its demethylation activity.[9]

References

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  1. ^ Pedersen, M.T. et al. "Histone Demethylases in Development and Disease" Cell Trends in Cell Biology. Nov, 2010;20,11:662-71.
  2. ^ Shi, Y., et al. "Histone Demethylation Mediated by the Nuclear Amine Oxidase Homolog LSD1" Cell. Dec 29, 2004;119:941-53
  3. ^ Wang, J. et al. (2009) The lysine demethylase LSD1 (KDM1) is required for maintenance of global DNA methylation. Nat. Genet. 41, 125–129
  4. ^ Wang, J. et al. (2007) Opposing LSD1 complexes function in developmental gene activation and repression programmes. Nature 446, 882–887
  5. ^ Kahl, P. et al. (2006) Androgen receptor coactivators lysine-specific histone demethylase 1 and four and a half LIM domain protein 2 predict risk of prostate cancer recurrence. Cancer Res. 66, 11341– 11347
  6. ^ Lim, S. et al. (2010) Lysine-specific demethylase 1 (LSD1) is highly expressed in ER-negative breast cancers and a biomarker predicting aggressive biology. Carcinogenesis 31, 512– 20
  7. ^ Metzger, E. et al. (2005) LSD1 demethylates repressive histone marks to promote androgen-receptor-dependent transcription. Nature 437, 436–439
  8. ^ Schulte, J.H. et al. (2009) Lysine-specific demethylase 1 is strongly expressed in poorly differentiated neuroblastoma: implications for therapy. Cancer Res. 69, 2065–2071
  9. ^ Wang, Y. et al. (2009) LSD1 is a subunit of the NuRD complex and targets the metastasis programs in breast cancer. Cell 138, 660–672
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