Heterochromatin is a tightly packed form of DNA or condensed DNA, which comes in multiple varieties. These varieties lie on a continuum between the two extremes of constitutive heterochromatin and facultative heterochromatin. Both play a role in the expression of genes. Because it is tightly packed, it was thought to be inaccessible to polymerases and therefore not transcribed; however, according to Volpe et al. (2002), and many other papers since, much of this DNA is in fact transcribed, but it is continuously turned over via RNA-induced transcriptional silencing (RITS). Recent studies with electron microscopy and OsO4 staining reveal that the dense packing is not due to the chromatin.
Cellular differentiation is the process in which a stem cell changes from one type to a differentiated one. Usually, the cell changes to a more specialized type. Differentiation happens multiple times during the development of a multicellular organism as it changes from a simple zygote to a complex system of tissues and cell types. Differentiation continues in adulthood as adult stem cells divide and create fully differentiated daughter cells during tissue repair and during normal cell turnover. Some differentiation occurs in response to antigen exposure. Differentiation dramatically changes a cell's size, shape, membrane potential, metabolic activity, and responsiveness to signals. These changes are largely due to highly controlled modifications in gene expression and are the study of epigenetics. With a few exceptions, cellular differentiation almost never involves a change in the DNA sequence itself. However, metabolic composition does get altered quite dramatically where stem cells are characterized by abundant metabolites with highly unsaturated structures whose levels decrease upon differentiation. Thus, different cells can have very different physical characteristics despite having the same genome.
Enhancer of zeste homolog 2 (EZH2) is a histone-lysine N-methyltransferase enzyme encoded by EZH2 gene, that participates in histone methylation and, ultimately, transcriptional repression. EZH2 catalyzes the addition of methyl groups to histone H3 at lysine 27, by using the cofactor S-adenosyl-L-methionine. Methylation activity of EZH2 facilitates heterochromatin formation thereby silences gene function. Remodeling of chromosomal heterochromatin by EZH2 is also required during cell mitosis.
Polycomb complex protein BMI-1 also known as polycomb group RING finger protein 4 (PCGF4) or RING finger protein 51 (RNF51) is a protein that in humans is encoded by the BMI1 gene. BMI1 is a polycomb ring finger oncogene.
Polycomb group RING finger protein 2, PCGF2, also known as MEL18 or RNF110, is a protein that in humans is encoded by the PCGF2 gene.
Polyhomeotic-like protein 2 is a protein that in humans is encoded by the PHC2 gene.
Polycomb group RING finger protein 1, PCGF1, also known as NSPC1 or RNF68 is a RING finger domain protein that in humans is encoded by the PCGF1 gene.
Trithorax-group proteins (TrxG) are a heterogeneous collection of proteins whose main action is to maintain gene expression. They can be categorized into three general classes based on molecular function:
- histone-modifying TrxG proteins
- chromatin-remodeling TrxG proteins
- DNA-binding TrxG proteins,
Bivalent chromatin are segments of DNA, bound to histone proteins, that have both repressing and activating epigenetic regulators in the same region. These regulators work to enhance or silence the expression of genes. Since these regulators work in opposition to each other, they normally interact with chromatin at different times. However, in bivalent chromatin, both types of regulators are interacting with the same domain at the same time. Bivalent chromatin domains are normally associated with promoters of transcription factor genes that are expressed at low levels. Bivalent domains have also been found to play a role in developmental regulation in pluripotent embryonic stems cells, gene imprinting and cancer.
PRC2 is one of the two classes of polycomb-group proteins or (PcG). The other component of this group of proteins is PRC1.
Cellular memory modules are a form of epigenetic inheritance that allow cells to maintain their original identity after a series of cell divisions and developmental processes. Cellular memory modules implement these preserved characteristics into transferred environments through transcriptional memory. Cellular memory modules are primarily found in Drosophila.
The human KDM2B gene encodes the protein lysine (K)-specific demethylase 2B.
Plants depend on epigenetic processes for proper function. Epigenetics is defined as "the study of changes in gene function that are mitotically and/or meiotically heritable and that do not entail a change in DNA sequence". The area of study examines protein interactions with DNA and its associated components, including histones and various other modifications such as methylation, which alter the rate or target of transcription. Epi-alleles and epi-mutants, much like their genetic counterparts, describe changes in phenotypes due to epigenetic mechanisms. Epigenetics in plants has attracted scientific enthusiasm because of its importance in agriculture.
Epigenetics of human development is the study of how epigenetics effects human development.
X chromosome inactivation (XCI) is the phenomenon that has been selected during the evolution to balance X-linked gene dosage between XX females and XY males.
H3K27me3 is an epigenetic modification to the DNA packaging protein Histone H3. It is a mark that indicates the tri-methylation of lysine 27 on histone H3 protein.
Thomas Jenuwein is a German scientist working in the fields of epigenetics, chromatin biology, gene regulation and genome function.
Polycomb repressive complex 1 (PRC1) is one of the two classes of Polycomb Repressive complexes, the other being PRC2. Polycomb-group proteins play a major role in transcriptional regulation during development. Polycomb Repressive Complexes PRC1 and PRC2 function in the silencing of expression of the Hox gene network involved in development as well as the inactivation of the X chromosome. PRC1 inhibits the activated form of RNA polymerase II preinitiation complex with the use of H3K27me. PRC1 binds to three nucleosomes, this is believed to limit access of transcription factors to the chromatin, and therefore limit gene expression.
Vincenzo Pirrotta is a biologist known for his work on Drosophila and polycomb group proteins. Born in Palermo, Italy, Pirotta migrated to the United States and enrolled at Harvard University. While at Harvard, he obtained undergraduate, graduate, and postdoctoral fellowships in physical chemistry and molecular biology. He later moved to Europe where he began studying gene regulation in bacteriophages and Drosophila. He was appointed assistant professor at the University of Basel in 1972. Pirotta returned to the United States, earning a full professorship at the Baylor College of Medicine in 1992. He then took up the position of professor of zoology at the University of Geneva in 2002, and in 2004 became a distinguished professor of molecular biology and biochemistry at Rutgers University.
Robert E. Kingston is an American biochemist who studies the functional and regulatory role nucleosomes play in gene expression, specifically during early development. After receiving his PhD (1981) and completing post-doctoral research, Kingston became an assistant professor at Massachusetts General Hospital (1985), where he started a research laboratory focused on understanding chromatin's structure with regards to transcriptional regulation. As a Harvard graduate himself, Kingston has served his alma mater through his leadership.
