The human Thyroid Hormone Receptor (TR) is a member of the nuclear receptor (NR) protein family. Members of this family of proteins are responsible for propagating the signals from specific hormone ligands by binding to specific DNA response elements and regulating the transcription of target genes. Like many NRs, TR is composed of multiple domains. The N-terminal region contains two zinc-coordinating modules that can bind DNA. The C-terminal region contains a ligand binding domain that can bind thyroid hormones, co-regulator proteins, and is also able to dimerize in solution. Depending on the DNA sequence and ligation status, TR can bind different DNA response elements and function as either a heterodimer, a homodimer, or a monomer. The DNA associated dimerization capability has a major impact on the NR function as a transcription regulator. We have investigated the structural basis behind the cooperativity observed for TR binding to different DNA response elements. We have found specific interactions between the DNA binding domains are able to facilitate the cooperative binding at certain DNA response elements. The DNA mediated cooperative binding is observed even in the isolated DNA binding domains of TR and is thus not a result of the dimerization interface in the ligand binding domain.