Dynamic Chromatin Loops and the Regulation of Gene Expression
Although we have a draft sequence of the human genome, little is known about how the chromatin fiber is packed in three-dimensional (3D) space, or how packing affects function (Jackson 2003). We know packing plays a major role; the rate of transcription of a typical gene can vary over eight orders of magnitude (Ivarie et al. 1983), but deleting local elements like promoters and enhancers reduces expression by less than 5000-fold in transient transfection assays where the 3D “context” is missing. Common sense suggests the fiber cannot be packed randomly, but elucidating what any underlying order might be has proved difficult. First, the foldings of the chromatin fiber have dimensions below the resolution (≈200 nm) of the light microscope (LM) and so can only be seen by electron microscopy (EM), but then the fixation required can distort structure. Second, DNA is so long and packed so tightly it breaks and/or aggregates easily on isolation. Third, chromatin is poised in a metastable state so small charge alterations trigger changes in structure and function, and replacing the natural environment with our buffers often promotes aggregation.
KeywordsTranscription Unit Chromatin Fiber Locus Control Region Histone Code Lampbrush Chromosome
Unable to display preview. Download preview PDF.
- Cook PR (2001) Principles of nuclear structure and function. Wiley, New York, pp 86–88, 182–184Google Scholar
- Pettijohn DE (1996) The nucleoid. In: Neidhardt FC, Curtiss R, Ingraham JL, Lin ECC, Brooks Low K, Magasanik B, Reznifoff WS, Riley M, Schaechter M, Umbarger HE (eds) Escherichia coli and Salmonella typhimurium: cellular and molecular biology. ASM Press, Washington, pp 158–166Google Scholar
- Pombo A, Cuello P, Schul W, Yoon J-B, Roeder RG, Cook PR, Murphy S (1998) Regional and temporal specialization in the nucleus: a transcriptionally-active nuclear domain rich in PTF, Octl and PIKA antigens associates with specific chromosomes early in the cell cycle. EMBO J 17:1768–1778PubMedCrossRefGoogle Scholar
- Saitoh Y, Laemmli UK (1978) From the chromosomal loops and the scaffold to the classic bands of metaphase chromosomes. Cold Spring Harbor Symp Quant Biol 58:755–765Google Scholar