Researchers in New York report in Nature that the epigenetic modification factors Parp1 and Tet2 are needed to regulate the epigenetic and chromatin status during somatic cell reprogramming to induced pluripotent stem cells. Parp1 regulates 5-methylcytosine modification and Tet2 aids in the oxidation of 5mC to5-hydroxymethylcytosine, and the researchers say that their "data support necessary but distinct roles for Tet2 and Parp1 in the regulation of epigenetic marks and local chromatin structure at pluripotency loci during an early stage of somatic cell reprogramming that precedes their transcriptional activation." Further, they say that Parp1 and Tet2 activity may be directly induced by the pluripotency factors Oct4, Sox2, Klf4, and c-Myc.
In a related News and Views article, Stanford's Kyle Loh and the Genome Institute of Singapore's Bing Lim write that the above paper "begins to clarify, at surprisingly early stages of the process and in unprecedented detail, the mechanisms by which cell types can be switched from one to another." Further, they add that if researchers "can ascertain the fundamental principles underlying such changes in cell identity, the terra incognita of cellular reprogramming may at last be mapped, expanding the ways in which diverse cell types can be generated for cell-based therapies."
Also in Nature, investigators led by Tak Mak from the Ontario Cancer Institute report that a mutation in the IDH1 gene, R132H, leads to an increased number of hematopoietic progenitors as well as splenomegaly and anemia in mice. Further, they write that the mutation leads to LSK and CRP cell accumulation in the bone marrow and the spleen. "We believe that the accumulations of these cells are most likely due to 2HG-induced DNA and histone hypermethylation that affect LSK cell division and/or differentiation," Mak and his colleagues add.