Chromatin Remodeling

Chromatin is a complex of double-stranded DNA and an octamer of histone proteins that are found inside of the nucleus of eukaryotic cells. The subunits of chromatin, which contain DNA surrounded by a single histone octamer, are called nucleosomes. There are two major types of chromatin: heterochromatin, which contains very tightly packaged DNA that cannot be unwound, and euchromatin, which contains loosely packaged DNA so that the DNA can be unwound and transcribed when gene expression is necessary. Chromatin functions to package DNA into a smaller volume, so that it can fit into the nucleus of a cell. Chromatin also serves to control the expression of genes in the euchromatin regions. In order for the genes to be expressed, this histone octomer must be modified. Modifications include methylation, phosphorylation, ubiquitination or acetylation by histone acetyltransferases or histone modifying complexes (13).

In order for transcription to occur, the promoter DNA from the targeted gene for transcription must be exposed so that the initiation complex, containing RNA polymerase II and TFII subunits, can bind to it. First, the DNA bends to allow the SNI/SNF or RSC complexes to move the histones surrounding the promoter site through either a sliding or translocation mechanism of the histone octamers. This is achieved through a nuclease attack on the nucleosome by the use of ATP, which serves as an energy releasing substrate (15). Once these histones are moved to a location away from the direction of transcription, there is a bulge formed in the DNA. Once this bulge is formed, the initiation complex can bind to the exposed promoter site on the DNA and transcription of the target gene can take place (14).

The work of Roger D. Kornberg on the mechanism of transcription by RNA polymerase II will be able to further redefine the process by which chromatin remodeling occurs. Kornberg has studied the subunits of RNA polymerase II extensively and their interactions with the TFII factors in order to form the initiation complex. From the findings of Kornberg’s studies, further investigation can be performed on chromatin to identify the role of the RNA polymerase II in the initial binding and remodeling of the DNA around promoter sites of the targeted genes. These studies will give a further advancement and a better understanding to the mechanism for chromatin remodeling.

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