Yeast Dot1 methyltransferase and its homologs (DOT1-Like or DOT1L) in higher organisms are uniquely responsible for histone H3 lysine 79 methylation (H3K79me) of the H3 core. The molecular consequences of H3K79me are poorly understood compared to the better studied modifications of the histone tails. However, dot1l loss-of-function experiments have demonstrated the critical role of DOT1L in early development of mammals, as well as its significance in the proper function of numerous cells and organs, including the immune system and the brown adipose tissue.
Mechanistically, Dot1 and DOT1L have been implicated in both positive and negative regulation of transcription through promoters and, more recently, enhancers, as well as DNA damage response. New studies described methyltransferase-independent functions of DOT1L in gene regulation. The increased volume of DOT1L-related publications begs for a better understanding of the connections between the biological functions of the protein and its enigmatic methyltransferase-dependent and -independent molecular mechanisms.
We would like to address the disconnect between the mechanistic studies of Dot1/DOT1L largely conducted in yeast and cell culture systems and the essential biological functions of DOT1L in cells and tissues of multicellular organisms.
We welcome original research manuscripts focusing on the molecular mechanisms of DOT1L in the context of early development and/or specialized cell, organ, and tissue functions. Also, manuscripts demonstrating the conservation of the molecular mechanisms identified in lower model organisms (yeast, nematodes, flies) to vertebrates and mammals are invited. Equally important are critical reviews of the existing literature that may find correlations between specific DOT1L mechanisms and biological contexts. Opinion pieces suggesting hypothetical models considering numerous existing publications and/or reconciling conflicting data are invited.
Yeast Dot1 methyltransferase and its homologs (DOT1-Like or DOT1L) in higher organisms are uniquely responsible for histone H3 lysine 79 methylation (H3K79me) of the H3 core. The molecular consequences of H3K79me are poorly understood compared to the better studied modifications of the histone tails. However, dot1l loss-of-function experiments have demonstrated the critical role of DOT1L in early development of mammals, as well as its significance in the proper function of numerous cells and organs, including the immune system and the brown adipose tissue.
Mechanistically, Dot1 and DOT1L have been implicated in both positive and negative regulation of transcription through promoters and, more recently, enhancers, as well as DNA damage response. New studies described methyltransferase-independent functions of DOT1L in gene regulation. The increased volume of DOT1L-related publications begs for a better understanding of the connections between the biological functions of the protein and its enigmatic methyltransferase-dependent and -independent molecular mechanisms.
We would like to address the disconnect between the mechanistic studies of Dot1/DOT1L largely conducted in yeast and cell culture systems and the essential biological functions of DOT1L in cells and tissues of multicellular organisms.
We welcome original research manuscripts focusing on the molecular mechanisms of DOT1L in the context of early development and/or specialized cell, organ, and tissue functions. Also, manuscripts demonstrating the conservation of the molecular mechanisms identified in lower model organisms (yeast, nematodes, flies) to vertebrates and mammals are invited. Equally important are critical reviews of the existing literature that may find correlations between specific DOT1L mechanisms and biological contexts. Opinion pieces suggesting hypothetical models considering numerous existing publications and/or reconciling conflicting data are invited.