ABSTRACT Support is requested for a Keystone Symposia conference entitled Gene Regulation: Celebrating 40 Years of the Enhancer, organized by Drs. Michael S. Levine and L. Stirling Churchman. The conference will be held in Santa Fe, New Mexico from January 23-27, 2022. Transcriptional control is at the heart of developmental and disease processes. Over decades, the field of gene regulation continues to elucidate how interactions between regulatory factors and elements in genomic DNA and nascent RNA control gene expression. This year, we celebrate the 40th anniversary of the enhancer, genomic DNA distal to gene promoters that controls transcription. Therapeutic strategies have struggled to target interactions between factors and cis-elements in DNA and RNA, but progress is now being made through the development of new drugs and new approaches. Furthermore, new concepts and technologies are revolutionizing our models of how transcription factors, chromatin and enhancers control genes. The conference will explore new paradigms such as the interplay between transcriptional condensates and genome topology and will stimulate debate on questions of mechanism and causality. This meeting aims to bring together innovators developing new ways to manipulate and probe transcription, from small molecules to single cell technology, with thought leaders working to define and elucidate gene regulatory mechanisms. Participants will attend sessions on transcriptional mechanisms, from structural details to molecular condensates, gene control in development, new technologies that observe and measure transcription in single cells and a session celebrating the discovery of the enhancer. It is anticipated that attendees, especially trainees, will leave the meeting excited by the field’s future and inspired by its history.