Horita D A, Ivanova A V, Altieri A S, Klar A J, Byrd R A
Structural Biophysics Laboratory, National Cancer Center at Frederick, MD 21702-1201, USA.
J Mol Biol. 2001 Mar 30;307(3):861-70. doi: 10.1006/jmbi.2001.4515.
The encapsulation of otherwise transcribable loci within transcriptionally inactive heterochromatin is rapidly gaining recognition as an important mechanism of epigenetic gene regulation. In the fission yeast Schizosaccharomyces pombe, heterochromatinization of the mat2/mat3 loci silences the mating-type information encoded within these loci. Here, we present the solution structure of the chromo domain from the cryptic loci regulator protein Clr4. Clr4 is known to regulate silencing and switching at the mating-type loci and to affect chromatin structure at centromeres. Clr4 and its human and Drosophila homologs have been identified as histone H3-specific methyltransferases, further implicating this family of proteins in chromatin remodeling. Our structure highlights a conserved surface that may be involved in chromo domain-ligand interactions. We have also analyzed two chromo domain mutants (W31G and W41G) that previously were shown to affect silencing and switching in full-length Clr4. Both mutants are significantly destabilized relative to wild-type.
将原本可转录的基因座包裹于转录失活的异染色质中，正迅速成为表观遗传基因调控的一种重要机制而受到认可。在裂殖酵母粟酒裂殖酵母中，mat2/mat3基因座的异染色质化使这些基因座内编码的交配型信息沉默。在此，我们展示了来自隐秘基因座调控蛋白Clr4的染色体结构域的溶液结构。已知Clr4可调控交配型基因座的沉默和转换，并影响着丝粒处的染色质结构。Clr4及其人类和果蝇同源物已被鉴定为组蛋白H3特异性甲基转移酶，这进一步表明该蛋白家族参与染色质重塑。我们的结构突出了一个可能参与染色体结构域 - 配体相互作用的保守表面。我们还分析了两个先前显示会影响全长Clr4的沉默和转换的染色体结构域突变体（W31G和W41G）。相对于野生型，这两个突变体均明显不稳定。
