The 30 nm chromatin fiber as a flexible polymer.

Our analysis of the data of van den Engh, Sachs, and Trask (Science 257, 1410 (1992)), for the dependence of the mean square distance between pairs of hybridization sites (< L2n >, micron 2) on the known genomic distance (n, bp) separating these sites on chromosome number 4 in G1 human fibroblast nuclei, shows that < L2n > is proportional to n2v with v = 3/5 for n < 1 Mbp. The v-value of 3/5 is characteristic of flexible polymer chains with excluded volume effects in dilute good solutions. Since the DNA concentration in nuclei is very high (ca. 1-10 mg/ml), and theory (Flory, J. Chem. Phys. 17, 303, 1949) predicts v = 1/2 for overlapping polymers, the finding of v = 3/5 means that the chromatin fibers do not overlap in interphase nuclei. The dependence of < L2n > on n for n < 4 Mbp is consistent with the model of large (approximately 6 Mbp, 3 microns diameter) loops of interphase chromatin attached to nuclear membrane sites. Using the constant (e.g., Widom, Ann. Rev. Biophys. Biophys. Chem. 18, 365 (1989)) and variable (Williams & Langmore, Biophys. J. 59, 606 (1991)) diameter fiber models, the Kuhn statistical segment of the 30 nm chromatin fiber was estimated to have a length of 196-272 nm with a corresponding DNA content of 21-37 kbp.(ABSTRACT TRUNCATED AT 250 WORDS)