The insulator binding protein CTCF associates with the nuclear matrix.
Nuclear DNA is organized into chromatin loop domains. At the base of these loops, matrix-associated regions (MARs) of the DNA interact with nuclear matrix proteins. MARs act as structural boundaries within chromatin, and MAR binding proteins may recruit multiprotein complexes that remodel chromatin. The potential tumor suppressor protein CTCF binds to vertebrate insulators and is required for insulator activity. We demonstrate that CTCF is associated with the nuclear matrix and can be cross-linked to DNA by cisplatin, an agent that preferentially cross-links nuclear matrix proteins to DNA in situ. These results suggest that CTCF anchors chromatin to the nuclear matrix, suggesting that there is a functional connection between insulators and the nuclear matrix. We also show that the chromatin-modifying enzymes HDAC1 and HDAC2, which are intrinsic nuclear matrix components and thought to function as corepressors of CTCF, are incapable of associating with CTCF. Hence, the insulator activity of CTCF apparently involves an HDAC-independent association with the nuclear matrix. We propose that CTCF may demarcate nuclear matrix-dependent points of transition in chromatin, thereby forming topologically independent chromatin loops that may support gene silencing.
Dunn
Katherine L
KL
Manitoba Institute of Cell Biology, University of Manitoba, Winnipeg, Manitoba R3E 0V9, Canada.
Zhao
Helen
H
Davie
James R
JR
D000595:Amino Acid Sequence; D001665:Binding Sites; D000076246:CCCTC-Binding Factor; D002843:Chromatin / Q000378:metabolism; D002945:Cisplatin / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D020868:Gene Silencing; D006655:Histone Deacetylases; D006801:Humans; D015530:Nuclear Matrix / Q000378:metabolism*; D012097:Repressor Proteins; D014157:Transcription Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; D002843:Chromatin; D004268:DNA-Binding Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D004247:DNA; D006655:Histone Deacetylases; D002945:Cisplatin