Tatiana Kutateladze, PhD
Professor
Contact Information:
University of Colorado Anschutz
Department of Pharmacology
Mail Stop 8303, RC1-South
12801 East 17th Ave
Aurora CO 80045
Phone: (303) 724-3593
Fax: (303) 724-3663
Email: [email protected]
Office: RC1-South,
L18-6100
My research focuses on understanding epigenetic mechanisms and deciphering the ‘epigenetic code/language’ – a network of chemical modifications or epigenetic marks that regulate how the human genome works without changing the DNA sequence. DNA in human cells is wrapped around histone proteins, forming a structure called chromatin, and epigenetic marks found in both DNA and histones alter the chromatin structure, accelerating or inhibiting fundamental DNA templated processes. Epigenetic marks in histones, known as posttranslational modifications (PTMs), adjust how tightly DNA is packaged and serve as docking sites for PTM-recognizing protein domains or ‘readers’. Binding of ‘readers’ to PTMs recruits various components of the epigenetic machinery to chromatin, affecting gene transcription, DNA replication and recombination, and DNA damage response.
Chromatin-associating complexes often contain multiple readers in one or several subunits that recognize different PTMs simultaneously. This leads to coordinated recognition or ‘combinatorial readout’ of a combination of PTMs and provides a lock-and-key type mechanism to ensure the right proteins and complexes bind to the correct genomic sites. The fine-tuned relationship between the epigenetic components represents one of the most intriguing concepts in modern chromatin biology, which we have only begun to explore. The spatial and temporal modulation of and crosstalk between epigenetic marks, ‘readers’, and the enzymes capable of depositing or removing these marks shape the epigenetic landscape, which ultimately directs which gene should be turned ‘on’ or ‘off’.
Misreading or misplacement of epigenetic marks has been linked to many human diseases, including autoimmune and developmental abnormalities, neurodegenerative disorders, and cancer. Therefore, understanding the molecular basis and biological roles of epigenetically driven interactions is essential not only for elucidating the fundamental principles of epigenetic regulation, but also for clarifying the etiology of epimutation-induced human diseases.
Among our major achievements, our lab is credited with establishing the molecular mechanisms and functional significance of methyllysine and acyllysine recognition and readout by a wide range of epigenetic readers and enzymatic complexes. These include the PHD, Tudor, PZP, YEATS, DPF, MBT, bromodomain, chromodomain, CW, BAH, chromoshadow, ET, ZZ, and PWWP readers and a number of methyltransferase, acetyltransferase and chromatin-remodeling complexes.
Chromatin-associating complexes often contain multiple readers in one or several subunits that recognize different PTMs simultaneously. This leads to coordinated recognition or ‘combinatorial readout’ of a combination of PTMs and provides a lock-and-key type mechanism to ensure the right proteins and complexes bind to the correct genomic sites. The fine-tuned relationship between the epigenetic components represents one of the most intriguing concepts in modern chromatin biology, which we have only begun to explore. The spatial and temporal modulation of and crosstalk between epigenetic marks, ‘readers’, and the enzymes capable of depositing or removing these marks shape the epigenetic landscape, which ultimately directs which gene should be turned ‘on’ or ‘off’.
Misreading or misplacement of epigenetic marks has been linked to many human diseases, including autoimmune and developmental abnormalities, neurodegenerative disorders, and cancer. Therefore, understanding the molecular basis and biological roles of epigenetically driven interactions is essential not only for elucidating the fundamental principles of epigenetic regulation, but also for clarifying the etiology of epimutation-induced human diseases.
Among our major achievements, our lab is credited with establishing the molecular mechanisms and functional significance of methyllysine and acyllysine recognition and readout by a wide range of epigenetic readers and enzymatic complexes. These include the PHD, Tudor, PZP, YEATS, DPF, MBT, bromodomain, chromodomain, CW, BAH, chromoshadow, ET, ZZ, and PWWP readers and a number of methyltransferase, acetyltransferase and chromatin-remodeling complexes.