DNA Methylation, Histone Modifications and Behaviour of AKAP95 during Mouse Oocyte Growth and Upon Nuclear Transfer of Foreign Chromatin into Fully Grown Prophase Oocytes

Abstract

HOFFMANN S., TOMASIK G., POLANSKI Z. 2012. DNA methylation, histone modifications and behaviour of AKAP95 during mouse oocyte growth and upon nuclear transfer of foreign chromatin into fully grown prophase oocytes. Folia Biologica (Kraków) 60: [163][164][165][166][167][168][169][170].The poor efficiency of mammalian cloning is due to inappropriate/incomplete epigenetic reprogramming of the donor chromatin. As the success in reprogramming of the donor nucleus may require activity of similar mechanisms which reprogram the chromatin in the course of gametogenesis, we decided to follow the status of some epigenetic markers in the late phase of oogenesis in mice, i.e. in prophase oocytes during their growth and after completion of the growth phase. Our analysis reveals an increase in the level of global DNA methylation starting in oocytes with diameters around 60Fm which was further elevated until completion of oocyte growth. A similar increase was observed in respect to the acetylation of histone H4. On the other hand, the methylation of histone H4 Arg3 was constantly high until the end of oocyte growth, although it differed between fully grown oocytes depending on the type of spatial chromatin organization. We have also studied the AKAP95 protein which was abundant at earlier stages but decreased in fully grown oocytes according to changes in their chromatin organization. The nuclear transfer of different types of donor nuclei with hypomethylated DNA into fully grown prophase oocytes did not increase the global level of methylation of transferred foreign chromatin, regardless if the recipient oocyte was devoid of its own nucleus or its nucleus was left intact. This suggests a major problem in the ability of recipient oocytes to modify donor DNA methylation.

Dynamic changes in protein interaction between AKAP95 and Cx43 during cell cycle progression of A549 cells

“…Cx43 has multiple biological functions, including regulation of cell proliferation and differentiation, and mainly acts via gap junction intercellular communication and signal transduction 20 21 22 23 24 25 26 . AKAP95 is primarily involved in DNA concentration and gene expression during mitosis 1 2 3 5 6 7 8 9 10 11 . Both Cx43 and AKAP95 affect cell cycle progression by regulating cyclin-CDK complexes 4 12 26 .…”

“…For example, AKAP95 has been shown to form complexes with p68 RNA helicase, RSK1, and MCM2 in the nuclear matrix; these interactions help regulate DNA replication 5 6 7 and maintain mRNA stability 8 in the rat brain. In addition, AKAP95 regulates mitosis 9 and apoptosis 10 via histone modifications. AKAP95 also regulates gene expression via MLL2-mediated histidine H3K4 methylation 11 .…”

Komórkowe mechanizmy zapewniające jakość żeńskich komórek rozrodczych ssaków

“…Dopełnieniem reprogramowania chromatyny oocytu w fazie wzrostu są modyfikacje białek histonowych, które, podobnie jak metylacja DNA, mogą regulować ekspresję genów [89,95]. Lista opisanych modyfikacji histonów zachodzących w tej fazie rozwoju oocytów jest już niezwykle długa i obejmuje zarówno modyfikacje potranslacyjne określonych aminokwasów w ogonach histonowych [96,97], jak i lokalne zastępowanie kanonicznych form histonów przez ich niekanoniczne odpowiedniki takie jak np. histon H3.3 [96].…”

The role of cyadox and recombinant growth hormone (rGH) on the promotion of growth through epigenetics

“…Additionally, different types of histone modi cation also have a signi cant impact on growth and development [22,23]. Tri-Methyl-Histone H3 (Lys4) (H3K4me3) and Acetyl-Histone H3 (Lys27) (H3K27ac) are generally linked to gene activation and growth and development of the body [24].…”

“…H3K27ac and H3K4me3 modi cations mainly occur around transcriptional start sites (TSSs) [25,26]. At present, the research of histone modi cation mainly focuses on the growth, maturation and activation of germ cells such as oocytes [23] and sperm [27], and the occurrence and development of diseases [28].…”