Nuclear Receptors: Type I and Type II Nuclear Receptor Pathway Steps

Nuclear receptors are a family of ligand activated transcription factors that are activated by steroid hormones, such as estrogen and various other lipid-soluble signals such as retinoic acid.

Type I Receptors: Ligand binds to the intracellular cytoplasmic receptor and then translocate to the nucleus as in the case of Estrogen receptor, Progesterone receptor

Type II Receptors: Ligand binds to the intracellular nuclear receptor located in the nucleus as in the case of Retinoic acid receptor, Thyroid receptor

Type I Nuclear receptor Pathway

Step 1: Ligand binding and detachment of Heat Shock Protein for Receptor-HSP complex

The receptor is bound to HSP in its inactive state. Ligand binding to the receptor releases HSP.

Step 2: Dimerization of receptor hormone complex

Step 3: Translocation to nucleus

Dimerized hormone receptor complex moves to the nucleus

Step 4: Binding of NR dimer to specific DNA sequence called Hormone response elements (HRE)

Step 5: Gene expression & cellular response

Binding of hormone to HRE induced transcription followed by translation of associated genes leading to cellular response

Type II Nuclear Receptor Pathway

Step 1: Ligand binding to Receptor causes dissociation of corepressor

The receptor located in the nucleus is bound to corepressor in its inactive state. This receptor corepressor complex is bound to specific DNA sequence or HREs even before ligand binding. Ligand binding to the receptor releases corepressor. Prior to ligand binding, receptor heterodimers are complexed with histone deacetylases (HDACs) and other co-repressors that keep target DNA in a tightly wound conformation, preventing exposure to transacting factors. Ligand binding results in co-repressor dissociation, chromatin derepression, and transcriptional activation.

Step 2: Recruitment of coactivator protein

Corepressors are replaced by coactivators. Coactivator complexes typically contain proteins with enzymatic functions, including histone acetyltransferases, that open up chromatin and facilitate activation of target genes

Step 3: Recruitment of proteins for transcription

Enzymes like RNA polymerase is recruited to the site for transcription.

Step 4: Gene expression and cellular response

This is followed by translation of associated genes leading to cellular response

This above video is a simplified summary for better understanding. Take care, Stay blessed. Thank you