TY - JOUR
T1 - Specificity landscapes of 40 R2R3-MYBs reveal how paralogs target different cis-elements by homodimeric binding
AU - Li, Tian
AU - Chen, Hao
AU - Ma, Nana
AU - Jiang, Dingkun
AU - Wu, Jiacheng
AU - Zhang, Xinfeng
AU - Li, Hao
AU - Su, Jiaqing
AU - Chen, Piaojuan
AU - Liu, Qing
AU - Guan, Yuefeng
AU - Zhu, Xiaoyue
AU - Lin, Juncheng
AU - Zhang, Jilin
AU - Wang, Qin
AU - Guo, Honghong
AU - Zhu, Fangjie
PY - 2025/4
Y1 - 2025/4
N2 - Paralogous transcription factors (TFs) frequently recognize highly similar DNA motifs. Homodimerization can help distinguish them according to their different dimeric configurations. Here, by studying R2R3-MYB TFs, we show that homodimerization can also directly change the recognized DNA motifs to distinguish between similar TFs. By high-throughput SELEX, we profiled the specificity landscape for 40 R2R3-MYBs of subfamily VIII and curated 833 motif models. The dimeric models show that homodimeric binding has evoked specificity changes for AtMYBs. Focusing on AtMYB2 as an example, we show that homodimerization has modified its specificity and allowed it to recognize additional cis-regulatory sequences that are different from the closely related CCWAA-box AtMYBs and are unique among all AtMYBs. Genomic sites described by the modified dimeric specificities of AtMYB2 are conserved in evolution and involved in AtMYB2-specific transcriptional activation. Collectively, this study provides rich data on sequence preferences of VIII R2R3-MYBs and suggests an alternative mechanism that guides closely related TFs to respective cis-regulatory sites. © 2025 The Author(s). iMeta published by John Wiley & Sons Australia, Ltd on behalf of iMeta Science.
AB - Paralogous transcription factors (TFs) frequently recognize highly similar DNA motifs. Homodimerization can help distinguish them according to their different dimeric configurations. Here, by studying R2R3-MYB TFs, we show that homodimerization can also directly change the recognized DNA motifs to distinguish between similar TFs. By high-throughput SELEX, we profiled the specificity landscape for 40 R2R3-MYBs of subfamily VIII and curated 833 motif models. The dimeric models show that homodimeric binding has evoked specificity changes for AtMYBs. Focusing on AtMYB2 as an example, we show that homodimerization has modified its specificity and allowed it to recognize additional cis-regulatory sequences that are different from the closely related CCWAA-box AtMYBs and are unique among all AtMYBs. Genomic sites described by the modified dimeric specificities of AtMYB2 are conserved in evolution and involved in AtMYB2-specific transcriptional activation. Collectively, this study provides rich data on sequence preferences of VIII R2R3-MYBs and suggests an alternative mechanism that guides closely related TFs to respective cis-regulatory sites. © 2025 The Author(s). iMeta published by John Wiley & Sons Australia, Ltd on behalf of iMeta Science.
KW - cis-elements
KW - DNA binding specificity
KW - homodimerization
KW - MYB family transcription factors
KW - paralogs
KW - regulatory noncoding genome
KW - transcriptional regulation
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UR - https://www.scopus.com/record/pubmetrics.uri?eid=2-s2.0-105002589234&origin=recordpage
U2 - 10.1002/imt2.70009
DO - 10.1002/imt2.70009
M3 - RGC 21 - Publication in refereed journal
SN - 2770-5986
VL - 4
JO - iMeta
JF - iMeta
IS - 2
M1 - e70009
ER -