Epigenetics and the estrogen receptor.
The position effect variegation in Drosophila and Schizosaccharomyces pombe, and higher-order chromatin structure regulation in yeast, is orchestrated by modifier genes of the Su(var) group, (e.g., histone deacetylases ([HDACs]), protein phosphatases) and enhancer E(Var) group (e.g., ATP [adenosine 5'-triphosphate]-dependent nucleosome remodeling proteins). Higher-order chromatin structure is regulated in part by covalent modification of the N-terminal histone tails of chromatin, and histone tails in turn serve as platforms for recruitment of signaling modules that include nonhistone proteins such as heterochromatin protein (HP1) and NuRD. Because the enzymes governing chromatin structure through covalent modifications of histones (acetylation, methylation, phosphorylation, ubiquitination) can also target nonhistone substrates, a mechanism is in place by which epigenetic regulatory processes can affect the function of these alternate substrates. The posttranslational modification of histones, through phosphorylation and acetylation at specific residues, alters chromatin structure in an orchestrated manner in response to specific signals and is considered the basis of a "histone code." In an analogous manner, specific residues within transcription factors form a signaling module within the transcription factor to determine genetic target specificity and cellular fate. The architecture of these signaling cascades in transcription factors (SCITs) are poorly understood. The regulation of estrogen receptor (ERalpha) by enzymes that convey epigenetic signals is carefully orchestrated and is reviewed here.
Leader
Jennifer E
JE
Kimmel Cancer Center, Department of Cancer Biology, Thomas Jefferson University, 233 South 10th Street, Philadelphia, PA 19107, USA.
Wang
Chenguang
C
Popov
Vladimir M
VM
Fu
Maofu
M
Pestell
Richard G
RG
D000107:Acetylation; D000818:Animals; D004330:Drosophila / Q000201:enzymology / Q000235:genetics; D044127:Epigenesis, Genetic; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D006655:Histone Deacetylases / Q000378:metabolism*; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D008745:Methylation; D011499:Protein Processing, Post-Translational; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D012568:Schizosaccharomyces / Q000201:enzymology / Q000235:genetics
D047628:Estrogen Receptor alpha; D006657:Histones; D018160:Receptors, Cytoplasmic and Nuclear; D011495:Histone-Lysine N-Methyltransferase; D006655:Histone Deacetylases