Structural Basis for the Binding Selectivity of Human CDY Chromodomains
The CDY (chromodomain on the Y) proteins play an essential role in normal spermatogenesis and brain development. Dysregulation of their expression has been linked to male infertility and various neurological diseases. Like the chromodomains of HP1 and Polycomb, the CDY chromodomains also recognize t...
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Published in | Cell chemical biology Vol. 27; no. 7; pp. 827 - 838.e7 |
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Main Authors | , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Ltd
16.07.2020
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Subjects | |
Online Access | Get full text |
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Summary: | The CDY (chromodomain on the Y) proteins play an essential role in normal spermatogenesis and brain development. Dysregulation of their expression has been linked to male infertility and various neurological diseases. Like the chromodomains of HP1 and Polycomb, the CDY chromodomains also recognize the lysine-methylated ARKS motif embedded in histone and non-histone proteins. Interestingly, the CDY chromodomains exhibit different binding preferences for the lysine-methylated ARKS motif in different sequence contexts. Here, we present the structural basis for selective binding of CDY1 to H3K9me3 and preferential binding of CDYL2 to H3tK27me3 over H3K27me3. In addition, we use a CDYL1/2-selective compound, UNC4850, to gain further insight into the molecular mechanisms underlying CDYL2 binding specificity. Our work also provides critical implications that CDYL1b's role in the regulation of neural development is dependent on its recognition of the lysine-methylated ARKS motif.
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•CDY1 is a specific reader of H3K9me3•CDYL1b and CDYL2 are preferential binders of H3K9me3 and H3tK27me3 over H3K27me3•UNC4850 is a specific small-molecule inhibitor toward CDYL1/2
CDY (chromodomain on the Y) proteins are able to recognize the lysine-methylated ARKS motif through their chromodomains. Dong et al. elucidate the binding selectivity of the CDY chromodomains using a combination of structural, chemical, and biochemical approaches. |
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ISSN: | 2451-9456 2451-9448 2451-9456 |
DOI: | 10.1016/j.chembiol.2020.05.007 |