Mixed lineage leukaemia histone methylases 1 collaborate with ERα to regulate HOXA10 expression in AML
| Autor: | Li‑Chao Fang, Jun Deng, Junsong Zheng, Jie Yao, Zai‑Lin Yang, Hui Huang, Yan Li |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
lcsh:Life
lcsh:QR1-502 Apoptosis Biochemistry lcsh:Microbiology Histones AML Gene Knockdown Techniques Promoter Regions Genetic Gene knockdown MSP methylation-specific PCR Estradiol Gene Expression Regulation Leukemic Reverse Transcriptase Polymerase Chain Reaction ALL acute lymphoblastic leukaemia Methylation HOXA10 MLL mixed lineage leukaemia histone methylase oestrogen receptor ChIP chromatin immunoprecipitation Histone Leukemia Myeloid Acute Disease Myeloid-Lymphoid Leukemia Protein AML acute myeloid leukaemia Protein Binding Expression of Concern ER oestrogen receptor mixed lineage leukaemia Blotting Western Biophysics HL-60 Cells Biology Response Elements S2 Cell Line Tumor Estrogen Receptor beta Humans Epigenetics ERE oestrogen response element Molecular Biology Estrogen receptor beta Homeodomain Proteins Original Paper NP40 Nonidet P40 Lysine Estrogen Receptor alpha LSD1 lysine-specific demethylase 1 Estrogens Cell Biology Histone-Lysine N-Methyltransferase lcsh:QH501-531 H3K4 H3 at lysine 4 Homeobox A10 Proteins Cancer research biology.protein HMT histone methyltransferase gene regulation Estrogen receptor alpha |
| Zdroj: | Bioscience Reports, Vol 34, Iss 6, p e00156 (2014) Bioscience Reports |
| ISSN: | 1573-4935 |
| Popis: | HOXA10, a homeobox-containing gene involved in definitive haematopoiesis, which implicated in the pathogenesis of AML (acute myeloid leukaemia), has been studied extensively. But the regulatory mechanism that drives HOXA10 expression is still unclear. In the present paper, HOXA10 regulated by MLL1 (mixed lineage leukaemia histone methylase 1) with an epigenetic way has been demonstrated. The HOXA10 promoter contains several EREs (oestrogen response elements), including ERE1 and ERE2, which are close to the transcription start site, and are associated with E2-mediated activation of HOXA10. It has been shown that knockdown of the ERα (oestrogen receptor α) suppresses E2-mediated activation of HOXA10. Similarly, knockdown of MLL1 suppresses activation of HOXA10 and is bound to the ERE of HOXA10 promoter in an E2-dependent manner by forming complex with ERα. Knockdown of ERα affects the E2-dependent binding of MLL1 into HOXA10 EREs, suggesting critical roles of ERα in recruiting MLL on the HOXA10 promoter. More interestingly, the methylation status of histone protein H3K4 (H3 at lysine 4) with E2 is much higher than without E2 treatment in leukaemia cell. On the contrary, the methylation status of HOXA10 promoter with E2 treatment is much lower, which elevate the HOXA10 expression. Moreover, with ERα knockdown, the H3K4 methylation level is also decrease in myeloid cell. Overall, it has been clearly demonstrated that HOXA10 is transcriptionally regulated by MLL1, which, in coordination with ERα, plays a critical role in this process with epigenetic way and suggests a potential anti-E2 treatment of AML. We find that E2 could elevate HOXA10 expression. We examine HOXA10 regulated by MLL1 with an epigenetic way. MLL1 bind to HOXA10 promoter through formatting complex with mainly ERα. |
| Databáze: | OpenAIRE |
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