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PHF6 Interacts with LMO2 During Normal Haematopoiesis and in Leukaemia and Regulates Gene Expression and Genome Integrity

Stanulovic, V. S.; Binhassan, S.; Dorrington, I.; Ward, D. G.; Hoogenkamp, M.

2020-08-18 cancer biology
10.1101/2020.08.18.255471 bioRxiv
Show abstract

The transcriptional mediator LIM domain only 2 (LMO2) forms a large multi-protein complex together with TAL1/LYL1, HEB/E2A, LDB1 and GATA. This complex regulates transcription from the onset of haematopoietic development and during differentiation. Chromosomal re-arrangements involving LMO and other members of the complex are causative for T-cell lymphoblastic leukaemia (T-ALL). We have identified Plant Homeodomain (PHD)-like Finger 6 (PHF6) as a new LMO2 interacting factor. Somatic mutations in PHF6 have been found to occur in several types of leukaemia. We show that PHF6 interacts with LMO2 during the initial stages of the haematopoietic development, myeloid differentiation and in T-ALL. The LMO2/PHF6 complex binds the DNA and regulates linage-specific gene expression. Additionally, a loss or reduction of LMO2 and PHF6 leads to chromosomal instability. PHF6 and LMO2 are required for maintaining levels of {gamma}H2AX and 53BP1, where PHF6 is important for {gamma}H2AX accumulation and LMO2 has a role in recruiting 53BP1 to {gamma}H2AX foci.

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"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.