6LUJ

Crystal structure of the SAMD1 SAM domain

Summary for 6LUJ

• Entry DOI: 10.2210/pdb6luj/pdb
• Descriptor: Atherin, SULFATE ION (3 entities in total)
• Functional Keywords: cpg-islands, transcription, pentamer, dna binding protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 5
• Total formula weight: 39024.87

Authors

Cao, Y.,Zhou, Y.,Wang, Z. (deposition date: 2020-01-29, release date: 2021-02-03, Last modification date: 2024-04-03)

Primary citation

Stielow, B.,Zhou, Y.,Cao, Y.,Simon, C.,Pogoda, H.M.,Jiang, J.,Ren, Y.,Phanor, S.K.,Rohner, I.,Nist, A.,Stiewe, T.,Hammerschmidt, M.,Shi, Y.,Bulyk, M.L.,Wang, Z.,Liefke, R.
The SAM domain-containing protein 1 (SAMD1) acts as a repressive chromatin regulator at unmethylated CpG islands.
Sci Adv, 7:-, 2021

PubMed Abstract: CpG islands (CGIs) are key regulatory DNA elements at most promoters, but how they influence the chromatin status and transcription remains elusive. Here, we identify and characterize SAMD1 (SAM domain-containing protein 1) as an unmethylated CGI-binding protein. SAMD1 has an atypical winged-helix domain that directly recognizes unmethylated CpG-containing DNA via simultaneous interactions with both the major and the minor groove. The SAM domain interacts with L3MBTL3, but it can also homopolymerize into a closed pentameric ring. At a genome-wide level, SAMD1 localizes to H3K4me3-decorated CGIs, where it acts as a repressor. SAMD1 tethers L3MBTL3 to chromatin and interacts with the KDM1A histone demethylase complex to modulate H3K4me2 and H3K4me3 levels at CGIs, thereby providing a mechanism for SAMD1-mediated transcriptional repression. The absence of SAMD1 impairs ES cell differentiation processes, leading to misregulation of key biological pathways. Together, our work establishes SAMD1 as a newly identified chromatin regulator acting at unmethylated CGIs.

PubMed: 33980486
DOI: 10.1126/sciadv.abf2229

Experimental method

X-RAY DIFFRACTION (1.12 Å)