DNMT3A and TET2 Compete and Cooperate to Repress Lineage-Specific Transcription Factors in Hematopoietic Stem Cells  

Oleh:

Xiaotian Zhang ; Jianzhong Su ; Jeong, Mira ; Myunggon Ko ; Yun Huang

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: Nature Genetics vol. 48 no. 09 (Sep. 2016), page 1014-1023.
Topik: Chromatin Immunoprecipitation; Gene Expression Profiling; Western Blot

Ketersediaan

Perpustakaan FK Nomor Panggil: N12.K Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

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Isi artikel

Mutations in the epigenetic modifiers DNMT3A and TET2 non-randomly co-occur in lymphoma and leukemia despite their epistasis in the methylation–hydroxymethylation pathway. Using Dnmt3a and Tet2 double-knockout mice in which the development of malignancy is accelerated, we show that the double-knockout methylome reflects regions of independent, competitive and cooperative activity. Expression of lineage-specific transcription factors, including the erythroid regulators Klf1 and Epor, is upregulated in double-knockout hematopoietic stem cells (HSCs). DNMT3A and TET2 both repress Klf1, suggesting a model of cooperative inhibition by epigenetic modifiers. These data demonstrate a dual role for TET2 in promoting and inhibiting HSC differentiation, the loss of which, along with DNMT3A, obstructs differentiation, leading to transformation.

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