The power of the (imperfect) palindrome: Sequence‐specific roles of palindromic motifs in gene regulation

• Published in: BioEssays Vol. 44; no. 4; pp. e2100191 - n/a
• Main Authors: Datta, Rhea R., Rister, Jens
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.04.2022
• Subjects: Animals; Base Sequence; cis‐regulatory motif; Deoxyribonucleic acid; DNA; enhancer; Gene Expression Regulation; Gene regulation; glucocorticoid; Humans; Mammals; Nucleotide sequence; palindrome; Palindromes; Receptors; Regulatory sequences; Repetitive Sequences, Nucleic Acid; rhodopsin; Signaling; steroid hormone receptor; Steroids; transcription factor; Transcription factors; Transcription Factors - genetics; rhodopsin; palindrome; transcription factor; enhancer; glucocorticoid; cis-regulatory motif; gene regulation; steroid hormone receptor
• ISSN: 0265-9247; 1521-1878
• DOI: 10.1002/bies.202100191

In human languages, a palindrome reads the same forward as backward (e.g., ‘madam’). In regulatory DNA, a palindrome is an inverted sequence repeat that allows a transcription factor to bind as a homodimer or as a heterodimer with another type of transcription factor. Regulatory palindromes are typically imperfect, that is, the repeated sequences differ in at least one base pair, but the functional significance of this asymmetry remains poorly understood. Here, we review the use of imperfect palindromes in Drosophila photoreceptor differentiation and mammalian steroid receptor signaling. Moreover, we discuss mechanistic explanations for the predominance of imperfect palindromes over perfect palindromes in these two gene regulatory contexts. Lastly, we propose to elucidate whether specific imperfectly palindromic variants have specific regulatory functions in steroid receptor signaling and whether such variants can help predict transcriptional outcomes as well as the response of individual patients to drug treatments. A palindrome reads the same forward as backward (compare top left to right). A regulatory palindrome is typically an imperfect inverted sequence repeat that is bound by a transcription factor homodimer, for example in mammalian steroid receptor signaling (bottom left) and Drosophila photoreceptor differentiation (bottom right). The underlying mechanisms remain incompletely understood.