Epigenetics and Chromatin Biology Group, Gupta Lab.
Animal House Facility, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai 410210, MH, India.
Exp Biol Med (Maywood). 2014 Oct;239(10):1335-9. doi: 10.1177/1535370214531869. Epub 2014 Apr 24.
Recent studies suggest the incorporation of histone variants into the chromatin regulate cellular proliferation, differentiation, and de-differentiation. We have earlier reported the increase of H2A.1 variant during sequential de-differentiation of hepatocyte to hepato-cellular carcinoma. Here, we decipher the alterations in expression of H2A.1 and H2A.2 variants during rat liver embryogenesis and regeneration. The expression of H2A.1 and H2A.2, at protein and mRNA level, does not alter in normal cellular proliferation associated with regeneration of liver post PH. In contrast, gradual decrease of H2A.1 with increase of H2A.2 is observed during differentiation of embryonic to adult liver. Furthermore, the accumulation of H2A.1 is higher in embryonic stem cells compared to normal adult liver. Collectively, these data support a strong correlation of H2A.1 expression with undifferentiated cells and overall epigenetic reprogramming in dedifferentiation and maturation of undifferentiated cells, rather than with normal cellular proliferation.
最近的研究表明，组蛋白变体的掺入到染色质中可以调节细胞的增殖、分化和去分化。我们之前的研究报道了在肝细胞向肝癌的连续去分化过程中 H2A.1 变体的增加。在这里，我们阐明了在大鼠肝胚胎发生和再生过程中 H2A.1 和 H2A.2 变体表达的变化。在与 PH 后肝再生相关的正常细胞增殖过程中，H2A.1 和 H2A.2 的蛋白和 mRNA 水平的表达没有改变。相比之下，在胚胎向成体肝的分化过程中，观察到 H2A.1 的逐渐减少和 H2A.2 的增加。此外，胚胎干细胞中 H2A.1 的积累量高于正常成年肝脏。总之，这些数据支持 H2A.1 表达与未分化细胞强烈相关，并且在未分化细胞的去分化和成熟过程中与整体表观遗传重编程相关，而不是与正常细胞增殖相关。
