5EGO

HOXB13-MEIS1 heterodimer bound to methylated DNA

Summary for 5EGO

• Entry DOI: 10.2210/pdb5ego/pdb
• Descriptor: Homeobox protein Meis1, DNA (5'-D(P*GP*TP*TP*GP*AP*CP*AP*GP*TP*TP*TP*TP*AP*(5CM)P*GP*AP*GP*G)-3'), DNA (5'-D(*CP*CP*TP*(5CM)P*GP*TP*AP*AP*AP*AP*CP*TP*GP*TP*CP*AP*AP*C)-3'), ... (5 entities in total)
• Functional Keywords: transcription factor, heterodimer, complex, bound to dna, transcription
• Biological source: Homo sapiens (Human); More
• Cellular location: Nucleus : O00470 Q92826
• Total number of polymer chains: 4
• Total formula weight: 25456.13

Authors

Morgunova, E.,Yin, Y.,Jolma, A.,Popov, A.,Taipale, J. (deposition date: 2015-10-27, release date: 2016-11-09, Last modification date: 2024-01-10)

Primary citation

Yin, Y.,Morgunova, E.,Jolma, A.,Kaasinen, E.,Sahu, B.,Khund-Sayeed, S.,Das, P.K.,Kivioja, T.,Dave, K.,Zhong, F.,Nitta, K.R.,Taipale, M.,Popov, A.,Ginno, P.A.,Domcke, S.,Yan, J.,Schubeler, D.,Vinson, C.,Taipale, J.
Impact of cytosine methylation on DNA binding specificities of human transcription factors.
Science, 356:-, 2017

PubMed Abstract: The majority of CpG dinucleotides in the human genome are methylated at cytosine bases. However, active gene regulatory elements are generally hypomethylated relative to their flanking regions, and the binding of some transcription factors (TFs) is diminished by methylation of their target sequences. By analysis of 542 human TFs with methylation-sensitive SELEX (systematic evolution of ligands by exponential enrichment), we found that there are also many TFs that prefer CpG-methylated sequences. Most of these are in the extended homeodomain family. Structural analysis showed that homeodomain specificity for methylcytosine depends on direct hydrophobic interactions with the methylcytosine 5-methyl group. This study provides a systematic examination of the effect of an epigenetic DNA modification on human TF binding specificity and reveals that many developmentally important proteins display preference for mCpG-containing sequences.

PubMed: 28473536
DOI: 10.1126/science.aaj2239

Experimental method

X-RAY DIFFRACTION (2.54 Å)