Defining the protein factors that directly recognize post-translational, 
covalent histone modifications is essential toward understanding the impact of 
these chromatin "marks" on gene regulation. In the current study, we identify 
human CHD1, an ATP-dependent chromatin remodeling protein, as a factor that 
directly and selectively recognizes histone H3 methylated on lysine 4. In vitro 
binding studies identified that CHD1 recognizes di- and trimethyl H3K4 with a 
dissociation constant (Kd) of approximately 5 microm, whereas monomethyl H3K4 
binds CHD1 with a 3-fold lower affinity. Surprisingly, human CHD1 binds to 
methylated H3K4 in a manner that requires both of its tandem chromodomains. In 
vitro analyses demonstrate that unlike human CHD1, yeast Chd1 does not bind 
methylated H3K4. Our findings indicate that yeast and human CHD1 have diverged 
in their ability to discriminate covalently modified histones and link histone 
modification-recognition and non-covalent chromatin remodeling activities within 
a single human protein.