Scientists at the University of Leicester have opened up a whole new approach to the therapeutic¹ intervention² for a family of anti-cancer drug targets, thanks to a completely new and unexpected finding. Professor Schwabe and his colleagues, Drs Watson, Fairall and Santos, have published their research this week in journal Nature detailing a new understanding of how transcriptional repression³ complexes work. Their work, which is based around determining atomic resolution structures of medically important bio-molecular complexes, has been ongoing⁴ for six years, and is currently funded through a £1.4 million grant from The Wellcome Trust.

Transcriptional regulatory complexes play an important role in the regulation of development, differentiation⁵, cancer and homeostasis（体内平衡） . Transcription is the process of creating a complementary RNA copy of a sequence of DNA⁶ and is the first step in the process of gene⁷ expression.

Professor John Schwabe, of the University of Leicester's Department of Biochemistry, said: "We have discovered a completely new and unexpected link between inositol（纤维糖） phosphate（碳酸盐） signalling (in this case IP4) and the regulation of histone（组蛋白） deacetylase（脱乙酰酶） enzymes⁹ and hence transcriptional repression or gene silencing.

"In simple terms, we have shown that IP4 acts as a natural signalling molecule¹⁰ to regulate histone deacetylase enzymes which play a key role in regulating gene expression. Apart from the considerable intellectual importance of understanding how transcription is regulated, repression complexes are important therapeutic targets for a number of cancers including several types of leukemia（白血病） .

"Our research identifies several new means to potentially target histone deacetylase enzymes therapeutically¹¹: either by using drugs to prevent IP4 binding¹² to the enzyme⁸ or by interfering¹³ with the pathway through which the body makes IP4. Thus this work opens up a whole new area of research with potential for new drugs and a new approach to targeting histone deacetylase enzymes."

Professor Schwabe said that this research is not only an exciting breakthrough in the field, but is also a technological¹⁴ feat¹⁵ relying on both the excellent research facilities in Leicester and the microfocus X-ray source at the Diamond Light Source in Oxfordshire.