Page 69 - AWSAR 2.0

all the genes bookmarked by each TF. In the illustration, you will notice that TF-1 bookmarks genes A, D, and H after it has identified the code word “TGATTTAT,” and yet it does not bookmark genes C and F,
although these genes also contain the same code word. Professor Aseem Ansari, from the University of Wisconsin– Madison, whose lab carried out deep sequencing of the fruit fly (Drosophila) genome, handed over the data to our laboratory to try and make sense of what’s going on.
Beyond the code. Since
looking at the code alone did not
help in identifying the selective
bookmarking preferences of
TFs, we decided to look beyond
the code. We picked up the introduction sections (promoter regions) of all genes that contained the code word “TGATTTAT” for binding to TF-1. We now focused not only on the code but also on the alphabets that immediately flanked the code word. Below is a short excerpt of the data we analyzed so you could analyze it yourself:
Gene A: CCGATGATTTATGGCC: bookmarked by TF-1
Gene C: AAAATGATTTATAAAA: not bookmarked by TF-1
Gene D: CCCCTGATTTATGCGA: bookmarked by TF-1
Gene F: AAAATGATTTATCGGA: not bookmarked by TF-1
Gene H: TGCATGATTTATAAAA: bookmarked by TF-1
Using thousands of such lists of words, we identified that whenever the code word in the introduction section was preceded by a string of A’s, TF-1 did not bookmark that gene chapter. This implied that simply having the code word was not enough; the context of
Dr Debostuti Ghoshdastidar || 45
the code word was also very important. That makes reading the genome book so similar to reading any of our other books, isn’t it? Let me explain. Let’s consider the code word is
“BEATEN” and use it in the following two sentences:
1) Vikas has always BEATEN his peers in school basketball matches. (beaten = defeated)
2) Vikas was badly BEATEN up by goons for standing up for the truth. (beaten = physically hurt)
The contexts of the words have completely changed the meaning of “beaten”; such words are called homonyms. Our genome book is filled with homonyms.
Homonyms in the genome: Just like the context changes the meaning of homonym words in a language, context changes the physical property of homonym DNA codes. Since DNA is not merely a string of letters, but a molecule, it has an important physical property called flexibility. Some letters make DNA flexible, while others make it rigid. For example,astringofletterA,asfoundinthe genes we described above, makes DNA rigid. Our TF-1 transcription factor didn’t bind its favorite code word (TGATTTAT) because the DNA preceding the code word was full of A, and therefore, was rigid. Thus, while homonym DNA codes themselves look identical, their context can change their flexibility. TFs, then, are not simply looking for a code but at the flexibility of the DNA around it. Smart, aren’t they? The findings from our study were recently published in the Journal of Nucleic Acids Research. In our studies, we have also come across other TFs that like binding to rigid DNA. Each of them has a unique preference. Therefore, we are now re-reading
A large protein complex called RNA polymerase serves as “eyes” to read through the instructions in the coding region. But, whether the RNA polymerase will read through a gene chapter or simply overlook it is directed by another family of proteins called transcription factors (TFs).