Wednesday, May 29, 2013

TALKING EPIGENETIC EVENTS: THE TET2 STORY

One of the gene that has marked its presence in the epigenetic region of the cell where gene Methylation belong, is TET2.
TET2, also known as TET (ten-eleven-translocation)2, belong to a family of genes that actually participate in methylation of genes.  Methylation of gene can block the expression of that gene, therefore TET2 is generally perceived as a Tumor suppressor gene.  TET2 seems to focus its attention somewhat exclusively on those genes that are involved in pluripotency particularly of the stem cell located in the Bone marrow.  The role of TET2 here to silence genes in order to influence somatic expression of genes in order to force stem cell differentiation in a specific lineage output.  That is if the body is Anemic with deficiency in red cells, the message is received at cell membrane, and possibly through the Wnt sent somehow to the TET2.  TET2 methylates gene blocking differentiation to platelets and white blood cells, forcing the stem cell to only express genes of red cell formation.

The Wnt assumption comes from the fact that TET2 is controlled by IDAX
again Ko et al:

"Here we show that IDAX (also known as CXXC4), a reported inhibitor of Wnt signalling7 that has been implicated in malignant renal cell carcinoma8 and colonic villous adenoma9, regulates TET2 protein expression. IDAX was originally encoded within an ancestral TET2 gene that underwent a chromosomal gene inversion during evolution, thus separating the TET2 CXXC domain from the catalytic domain. The IDAX CXXC domain binds DNA sequences containing unmethylated CpG dinucleotides, localizes to promoters and CpG islands in genomic DNA and interacts directly with the catalytic domain of TET2 "

The Wnt also will send a consensus message to other stem cell through the NOTCH so that the message is clear to what stem cells should be doing!

The IDAX has now been a target for therapy in order to further regulate TET2 in those MDS and leukemias in which Mutation at TET2 seems to contribute to malignant proliferation.   All in all, TET2 seems to belong to the molecules that gives stem cells potential of creating new combination of proteins!

OF NOTE TOO MUCH OF IDAX RECRUIT CASPASES AND LEADS TO CELL DEATH.

KO et al: " Unexpectedly, IDAX expression results in caspase activation"  SO BE CAREFUL HANDLING THESE STUFF !

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