Aspects of large-scale chromatin structures in mouse liver nuclei can be predicted from the DNA sequence

Abstract

The large amount of non-coding DNA present in mammalian genomes suggests that some of it may play a structural or functional role. We provide evidence that it is possible to predict computationally, from the DNA sequence, loci in mouse liver nuclei that possess distinctive nucleosome arrays. We tested the hypothesis that a 100 kb region of DNA possessing a strong, in-phase, dinucleosome period oscillation in the motif period-10 non-T, A/T, G, should generate a nucleosome array with a nucleosome repeat that is one-half of the dinucleosome oscillation period value, as computed by Fourier analysis of the sequence. Ten loci with short repeats, that would be readily distinguishable from the pervasive bulk repeat, were predicted computationally and then tested experimentally. We estimated experimentally that less than 20% of the chromatin in mouse liver nuclei has a nucleosome repeat length that is 15 bp, or more, shorter than the bulk repeat value of 195 ± bp. All 10 computational predictions were confirmed experimentally with high statistical significance. Nucleosome repeats as short as 172 ± 5 bp were observed for the first time in mouse liver chromatin. These findings may be useful for identifying distinctive chromatin structures computationally from the DNA sequence.

Direct measurements of the nucleosome-forming preferences of periodic DNA motifs challenge established models

“…Yet, the seemingly unrelated motifs period-10 motifs AA/TT/TA and VWG/CWB appear to correlate with nucleosome positioning (11,13) and chromatin structure/function (15,16), respectively. How might these findings be reconciled?…”

“…Generally, wherever the count of VWG/CWB in a 100-bp window is high, the count of TA is low, and vice versa. Thus, in large regions of DNA where period-10 VWG/CWB oscillated regularly, shown to correlate with the formation of regular nucleosome arrays (15), period-10 TA also oscillated regularly.

Figure 4.Anti-correlation of the VWG/CWB and the TA signals in the MADA gene DNA sequence.

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In Silico Approaches Reveal the Potential for DNA Sequence-dependent Histone Octamer Affinity to Influence Chromatin Structure in Vivo

“…Most cell types have repeats in the 180-200 bp range 2 although this property is an "average" value for any cell type and within a single nucleus substantial variation in repeat length can occur. 29 Some insight into the factors that can influence chromatin repeat lengths in vitro has been derived from studies using nucleosome assembly systems extracted from embryonic tissues. [30][31][32] Our studies present an insight into how changes in chromatin repeat length could be interpreted by the underlying positioning data inherent in the DNA sequence, and expressed in terms of an alteration to chromatin organisation.…”

Sequence Information Encoded in DNA that May Influence Long-Range Chromatin Structure Correlates with Human Chromosome Functions

“…Recently, our laboratory showed that the triplet motif non-T, A/T, G (VWG) [16] or its complement (CWB) contributes to a genomic DNA code for chromatin structure, at least in higher organisms where histone H1 is present [17] . There are ten VWG/CWB trinucleotides: AAG, GAG, CAG, ATG, GTG, CTG, CAT, CAC, CTT, and CTC.…”

“…We used the mouse genomic DNA sequence to test our ability to computationally predict 100 kb regions of the mouse genome that exhibit unusually short (<185 bp) nucleosome array periodicities, compared with the bulk chromatin periodicity of 195±5 bp, in mouse liver nuclei. We tested each prediction experimentally and showed that we were able to correctly predict 10 out of 10 nucleosome array periodicities ±5 bp ( P -value<10 −7 ) [17] . Our findings suggested that it should now be possible, for the first time, to predict which regions of the human genome have more limited or defined, rather than random or highly variable, chromatin structures.…”