For most proteins, the synthesis rate increases in direct proportion to the cell volume because also the limiting machinery for transcription and translation, including RNA polymerase and ribosomes, increases in abundance as cells get bigger. This means that more proteins are produced when the cell grows bigger and thereby, stable protein concentrations can be maintained. However, for histone proteins, which bind to the DNA to pack it into the nucleus, this machinery-limited regulation is not appropriate, because rather than constant concentrations, the cell needs histone amounts that are proportional to the DNA content.
If too many histone proteins are produced but the DNA amount stays the same, the DNA gets more compacted, and highly condensed DNA forms an obstacle for many cellular processes. In contrast, too few histones would lead to loosely packed DNA that can be processed without any control. Both scenarios would harm the integrity and survival of the cell.
Thus, to maintain the right number of histones, cells couple histone production temporally to DNA duplication so that they are only produced when they are needed. But how do they ensure that the right amount of histones is produced, even though protein production rate during S-phase depends on cell size and growth rate, and S-phase duration varies in different environmental conditions? We aim to understand how cells can produce the right number of histones independently of their size and how this regulation is affected by different environmental conditions. By understanding the cell-size-dependent regulation of histones in the budding yeast Saccharomyces cerivisae and the green alga Chlamydomonas reinhardtii, we expect to reveal regulatory processes that are broadly used by cells to adjust their protein content according to the requirements that go along with changes in cell size.
Chatzitheodoridou, D., Bureik, D., Padovani, F., Nadimpalli, K.V. & Schmoller., K.M. (2024) Decoupled transcript and protein concentrations ensure histone homeostasis in different nutrients, The EMBO Journal, 43: 5141 - 5168
Claude, K.-L., Bureik, D., Chatzitheodoridou, D., Adarska, P., Singh, A. & Schmoller, K.M. (2021) Transcription coordinates histone amounts and genome content, 12, 1-17
