PHF6: a conductor of HSC self-renewal
Courtesy of Satoru Miyagi, Ph.D.
(A) Strategy for competitive repopulating assays using the Mx1-Cre system. Mx1-Cre and Mx1-Cre;Phf6fl/y mice were injected with pIpC at 7 weeks of age and BM cells were harvested for competitive transplantation at 12 weeks of age. Ly5.2 BM cells were transplanted into lethally irradiated Ly5.1 recipient mice along with the same number of Ly5.1 WT BM cells. (B) The chimerism of donor cells in peripheral blood after transplantation.
Phf6 (plant homeodomain-like finger gene 6) is located on the X-chromosome and encodes a chromatin-binding protein with two zinc finger domains. Therefore, PHF6 is implicated to regulate gene transcription . PHF6 is known to disease gene for one of the X-linked intellectual disability disorder; Börjeson-Forssman-Lehmann syndrome (OMIM#301900) . In addition, it is reported that some patients of hematopoietic stem cell disorders (T-cell acute lymphoblastic leukemia, acute myeloid leukemia, myelodysplastic syndrome, etc.) have PHF6 inactivating mutations [3-5].
|Depositor||:||Satoru Miyagi, Ph.D.
Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University
(at the time of the strain deposition)
|References||:||||Todd MA, Ivanochko D, Picketts DJ.
PHF6 Degrees of Separation: The Multifaceted Roles of a Chromatin Adaptor Protein.
Genes (Basel).; 6(2):325-52, 2015.
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Mutations in PHF6 are associated with Börjeson-Forssman-Lehmann syndrome.
Nat Genet.; 32(4):661-5, 2002.
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PHF6 mutations in T-cell acute lymphoblastic leukemia.
Nat Genet.; 42(4):338-42, 2010.
|||Van Vlierberghe P, Patel J, Abdel-Wahab O, Lobry C, Hedvat CV, Balbin M, Nicolas C, Payer AR, Fernandez HF, Tallman MS, Paietta E, Melnick A, Vandenberghe P, Speleman F, Aifantis I, Cools J, Levine R, Ferrando A.
PHF6 mutations in adult acute myeloid leukemia.
Leukemia.; 25(1):130-4, 2011.
|||Mori T, Nagata Y, Makishima H, Sanada M, Shiozawa Y, Kon A, Yoshizato T, Sato-Otsubo A, Kataoka K, Shiraishi Y, Chiba K, Tanaka H, Ishiyama K, Miyawaki S, Mori H, Nakamaki T, Kihara R, Kiyoi H, Koeffler HP, Shih LY, Miyano S, Naoe T, Haferlach C, Kern W, Haferlach T, Ogawa S, Yoshida K.
Somatic PHF6 mutations in 1760 cases with various myeloid neoplasms.
Leukemia.; 30(11):2270-2273, 2016.
|||Miyagi S, Sroczynska P, Kato Y, Nakajima-Takagi Y, Oshima M, Rizq O, Takayama N, Saraya A, Mizuno S, Sugiyama F, Takahashi S, Matsuzaki Y, Christensen J, Helin K, Iwama A.
The chromatin-binding protein Phf6 restricts the self-renewal of hematopoietic stem cells.
Blood.; 133(23):2495-2506, 2019.
Contact: Saori Mizuno, Ph.D.
Experimental Animal Division, RIKEN BioResource Research Center
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