HOTAIR


HOTAIR is a human gene located on chromosome 12. It is the first example of an RNA expressed on one chromosome that has been found to influence transcription on another chromosome.

Gene and transcribed RNA product

The HOTAIR gene contains 6,232 bp and encodes 2.2 kb long noncoding RNA molecule, which controls gene expression. Its source DNA is located within a HOXC gene cluster. It is shuttled from chromosome 12 to chromosome 2 by the Suz-Twelve protein.

Function

The 5′ end of HOTAIR interacts with a Polycomb-group protein Polycomb Repressive Complex 2 and as a result regulates chromatin state. It is required for gene-silencing of the HOXD locus by PRC2. The 3′ end of HOTAIR interacts with the histone demethylase LSD1.
It is an important factor in the epigenetic differentiation of skin over the surface of the body. Skin from various anatomical positions is distinct, e.g. the skin of the eyelid differs markedly from that on the sole of the foot.

Clinical significance

HOTAIR is highly expressed in metastatic breast cancers. High levels of expression in primary breast tumours are a significant predictor of subsequent metastasis and death. This is partially due to HOTAIR-mediated overexpression of the HER2 oncogene through sequestration of miR-331-3p, which is a negative regulator of HER2 expression. In cells, especially those that over express PRC2, the prevention of HOTAIR expression leads to a reduction in invasive potential of that cell. It is also involved in esophageal squamous cell carcinoma.