![pallaki x 90 sk pallaki x 90 sk](https://c.saavncdn.com/020/Best-of-2016-Hindi-2016-500x500.jpg)
In particular, it frequently co-resides with the repressive markH3K27me3 in the promoters of critical differentiation-specific genes that are transcriptionallyinactive in ES cells (Figure 1B). H3K4me3 levels are positively correlated with gene expression levels (Figure 1A).Īlthough H3K4me3 is clearly associated with actively transcribed genes, however,studies have demonstrated that H3K4me3 is localized around the transcriptioninitiation sites of numerous unexpressed genes in human ES cells, primaryhepatocytes, and several other cell types. In fact, H3K4me3 is required to induce critical developmental genesin animals, including Drosophila and several mammals, and is importantfor animal embryonic development. H3K4me3 occupies as many as 75% of all human gene promoters in several cell types(e.g., ES cells), indicating that it plays a critical role in mammalian geneexpression. In this review, we summarize the recent progress in understanding the functions ofH3K4 methyltransferases and demethylases in modulating stem cells’ fates. In particular, the JARID1 family of histone demethylases(JARID1A−D) can erase H3K4me3 and H3K4me2. Subsequently, many Jumonji (JmjC) domain-containing histone demethylaseshave been discovered.
![pallaki x 90 sk pallaki x 90 sk](https://i.ytimg.com/vi/rGK4q-fn9Bw/maxresdefault.jpg)
LSD1 was reported to also have H3K9 demethylation activity. LSD1 and LSD2 remove methyl groups from di- andmonomethylated H3K4 but are unable to demethylate trimethylated H3K4. The first identified lysine-specific demethylase 1, together with LSD2, belongs tothe polyamine oxidase family. Similar to other histone modifications, histone methylation can be reversed byhistone demethylases (HDMs). Methylated lysines exist in three forms: mono-, di- and tri-methylation(me1, me2, and me3). For example, H3K4 methylation is mediated by several SET domain-containing methyltransferases, including mixedlineage leukemia 1–5 (MLL1−5), SET1A/B, SET7/9, SET and MYNDdomain-containing protein 1–3 (SMYD1−3), Absent, Small, or Homeotic1-like (ASH1L), SET domain and Mariner transposase fusion gene (SETMAR), and PRdomain zinc finger protein 9 (PRDM9). Histone lysine methylation is generated by a battery of histone methyltransferases(HMTs) that transfer the methyl group from S-adenosylmethionine to specific lysineresidues. In general, histone H3 lysine 4(H3K4), H3K36, and H3K79 methylation are gene activation marks, whereas H3K9, H3K27,and H4K20 methylation are gene-repressive modifications. Rather, thedifferent methylation status of specific histone lysines can serve as a uniqueplatform for recruiting methylation “reader” proteins that activate orrepress genes’ transcriptional activity. Unlike acetylation, the methylation does not change the charge of lysine residuesand thus has a minimal direct effect on DNA-histone association. Histone lysine methylation has been widely accepted as a key epigenetic modification. Notably, the functions of epigenetic modifiers in stem cell fate decisionhave been intensively studied. In fact, a recent study demonstrated that the histone modification andDNA methylation profiles differ in one-third of the genome between human embryonicstem (ES) cells and primary fibroblasts, indicating that such remarkable epigenetic difference may serve as amajor molecular mechanism in determining cellular characteristics of these two celltypes.
![pallaki x 90 sk pallaki x 90 sk](https://i.ytimg.com/vi/YtC5ett0fcE/hqdefault.jpg)
However, because the reprogramming efficiency of these four factors islow, it is evident that additional layers of co-regulatory mechanisms exist besidestranscription factor-driven regulation. Since Yamanaka and colleagues demonstrated thatthe four DNA-binding transcription factors Oct4, Sox2, c-Myc, and Klf4 transformfibroblasts into a type of pluripotent cells known as induced pluripotent stemcells, the importance of transcription factors in cellular reprogramming has beenmore recognized. Stem cells have long-term self-renewing activity and can commit to multiple celltypes upon differentiation signals.