N

The first column is the position along a Pax6 binding site as experimentally determined;the next 4 positions give the frequency of each nucleotide in this position observed among 47 tested sequences bound by this TF. The last column gives the predominant nucleotide (if any). N indicates no predominant nucleotide, S is C or G predominates, W is A or T predominates. Source: Transfac data base: http://bioinformatics.weizmann.ac.il/transfac/)

The first column is the position along a Pax6 binding site as experimentally determined;the next 4 positions give the frequency of each nucleotide in this position observed among 47 tested sequences bound by this TF. The last column gives the predominant nucleotide (if any). N indicates no predominant nucleotide, S is C or G predominates, W is A or T predominates. Source: Transfac data base: http://bioinformatics.weizmann.ac.il/transfac/)

and off of REs in this way can alter the number and nature of REs, or their arrangement, near a given gene. Therefore, even if the coding part of a gene is not altered, its usage may be.

Sequence bears other sorts of expression-control information. CpG regions (CpG rather than CG to indicate successive nucleotides along a strand rather than C-G base pairs between strands) located just 5' to a gene can be enzymatically methylated to make the region unavailable for binding by regulatory factors. Histone modification by acetylation or methylation appears, respectively, to allow or suppress access by transcriptional machinery and hence to affect gene expression (e.g., Bird 2001; Struhl 2001).

Linkage relationships can present a kind of arrangement-based information that allows clusters of genes to be coordinately regulated via the information in shared REs. An LCR can be the initiation point for a process that moves down the chromosome, for example, by starting a competitive or sequential binding process that activates downstream genes. Or each gene can have its own copy (or copies) of the same RE(s). There are many examples, including coregulated, corelevant cellular housekeeping genes (Lercher et al. 2002). However, linked genes may be expressed together without being regulated by the same mechanism, and not all the genes

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