Requirement Of The Histone Demethylase LDS1 In GATA2-mediated Epigenetic Mechanisms During Erythroid Cell Differentiation In Erythroleukemia

Previous studies have shown that LSD1 is involved in activation and inhibition of gene transcription, plays an important role in the occurrence and development of diseases like leukemia, and is a potential target gene of leukemia. Therefore, we make a further study on LSD1.LSD1 is the first histone lysine-specific demethylase found in human. LSD1. It contains a C-terminal amine oxidase domain, a N-terminal SWIRM domain and a Tower domain which is a two-parallel structure extended from amine oxidase domain, and divide amine oxidase domain into catalytic active center and FAD binding domain. Most of the proteins interacting with chromosome contain SWIRM domain.It is possible that LSD1 is involved in GATA switch which plays an important role in hematopoietic differentiation, so we wonder how LSD1 performs in the occurrence and development of leukemia, and which GATA factor participates in the interaction with LSD1. To further understand the mechanism by which LSD1 regulates the transcription of GATA2 and LSD1 binding site in genomic DNA, we could further investigate LSD1-mediated epigenetic modification of hematopoietic development.With the results of IP we have confirmed there is protein-protein interaction between TAL1 and GATA2 which also exists between TAL1 and GATA2 in MEL cells. We have found that GATA2 bound to the SWIRM domain of LSD1 through GST pull down. The results of western blot showed the expression of both of GATA2 and LSD1 were decreased, while the expression of GATA1 was increased, which means there might not be interaction between LSD1 and GATA1, unlike the interaction between LSD1 and GATA2. The expression of both of GATA2 and LSD1 are decreased during the differentiation of hematopoietic system, which suggests LSD1 plays a negative role in differentiation of hematopoietic system.