Question

You isolate some DNA and Monitor it dimensions. This particular DNA has a great number of base pairs per turn of the helix than normal. How would you describe its conformation and explain how this is corrected in normal cellular activity such as transcription?

Answer 1

Chromatin structure modulates gene expression. Gene-rich regions are enriched in “open” chromatin (30 nm fibers and a lesser number of base pairs per turn) while heterochromatin (a greater number of base pairs per turn) has a “closed” structure and harbors regions that are not transcribed.

Chromatin packaging is regulated by the following methods:

1) at the nucleosome level where histone modifications (like acetylation or methylation) or histone variants direct either active transcription or gene repression. For instance, Histone methylation occurs on lysine (K) and Arginine (R) residues. Histone lysines can be mono- (me1), di- (me2), or trimethylated (me3). H3K4 methylation produces active chromatin while H3K9 dimethylation produces inactive chromatin.

2) In eukaryotes, DNA methylation by DNA methyltransferases at the cytosine bases usually immediately adjacent to a guanine nucleotide converts cytosine to 5-methylcytosine. Methylation most likely blocks the promoters at transcription factor binding sites and represses gene expression.

3) A nucleosome core particle comprises of eight histone proteins (two each of H2A, H2B, H3 and H4) and 146 base pairs of double-stranded DNA. The H2A.Z is a H2A variant and is enriched near inactive gene promoters. SWR1 is a chromatin remodeling complex that catalyzes an ATP-dependent exchange of H2A in the nucleosome for H2A.Z.