Biochemistry Online: An Approach Based on Chemical Logic

Biochemistry Online




Last Updated: 03/30/16

Learning Goals/Objectives for Chapter 5D:  After class and this reading, students will be able to

  • describe general mechanisms of how a gene for a given protein might be negatively and positively regulated at the level of gene transcription;
  • describe the structure/function/role of promoters, response elements, RNA polymerase, transcription factors, nucleosomes, histone proteins, epigenetic modifications of DNA in gene transcription;
  • explain the differences (structural, Kds) between specific and nonspecific binding of a ligand to a macromolecule, at the structural level;
  • describe the structural features of both proteins and DNA that result in specific and nonspecific binding;
  • describe and give examples of how post-translational modifications of proteins and epigenetic modifications of DNA can alter gene expression;
  • explain how the apparent Kd for a protein binding to DNA can be altered by the presence of another protein bound to DNA at a proximal site
  • describe the basis of RNA interference in gene expression


D15.  ENCODE:  Encyclopedia of DNA Elements

ENCODE is a public research consortium, sponsored by the National Human Genome Research Institute (NHGRI),  who goals is to identify all functional elements in the human genome sequence. In September 2012, scientists involved in the project simultaneously published multiple papers the have significantly altered our understanding of how information about gene regulation is encoded into the genome.  Scientists have now identified how function is encoded into most of the genome, a far cry from the early notion that nonprotein-coding DNA sequences, which comprise 98% of the genome, is irrelevant or junk DNA.  Investigators used a variety of techniques to link structure to specific regions of the genome including sequencing of transcribed RNA from different types of cells, assessing senstivity/protection of DNA to an endonuclease, DNase 1, which gives information on DNA packing in chromatin and accessibility to transcription factors (see figure below),  and mapping long range effects of distal enhancers on gene transcription,.

Figure: DNase 1 Sensitivity of Nucleosome Bound and Free DNA

DNase 1 Sensitivity DNA

Here are some of the consortium's significant findings:

This list clearly shows that genetic information encoded by the linear sequence of DNA ("1 bit" per 3.2 billion base pairs) is only a first approximation of the available information which is encoded by small contiguous stretches of DNA (as found in promoters), by loops distal to promoters (enhancers), chemical modification of DNA (methylation) and DNA binding proteins (methylation, acetylation, phosphorylation), and accessibility of DNA sequences to transcriptional regulators (RNA, protein) and packaging proteins (histones).    All of these must be considered as we try to decode the human genome.

Just as a contrast, we have already discussed how proteins also have additional information elements other than their primary sequence which has the information necessary for protein folding.  Short linear stretches of amino acids also act as signaling elements.  These included N-terminal signal sequences which help locate proteins in the outside of the cell, degradation sequences (regions enriched in PEST amino acids - single letter code), signals that have evolved to encourage or discourage homodimer, heterodimer or nonspecific aggregation, as well as sequences that lead to specific post-translational modifications.  Biological macromolecules (proteins and nucleic acids) are surely information macromolecules.


Return to Chapter 5D: Binding and the Control of Gene Transcription

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 Archived version of full Chapter 5D:  Binding and the Control of Gene Transcription


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