What stands behind the message sent by histone PTMs?
Over the last 60 years, research has shed light on histone PTMs and their role in all DNA-templated processes. In the last decade, novel methodologies, such as genome-wide sequencing approaches, have paved the way toward understanding how their deposition, presence, and/or removal regulate genome function. In their recent review, Prof. Robert Schneider and Dr. Adam Burton from Helmholtz Munich look at the cause and consequence of histone PTMs for genome function.
Each of our body cells contains our complete hereditary information encoded in around 30,000 individual genes. Each gene serves as a plan for a protein that can be produced during a process called gene expression. The genes sit on a roughly 2 m long DNA string, which is densely folded and safely stored inside the nucleus of each cell.
Chromatin: friend and foe of transcription
The packaging structure of the DNA is called chromatin and it is important to fit the long-range of genetic material into the tiny nucleus of a cell. The chromatin structure is also an essential means of regulating DNA-templating processes, including transcription – the fundamental process that generates transportable messenger RNA molecules, which transport the information of the genes on how the specific proteins need to look like to the protein production machineries – and post-translational histone modifications (PTMs) influence how the DNA is packaged.
Chromatin consists of a repeating array of nucleosomes looking like beads on a string. One nucleosome consists of two copies of H2A, H2B, H3, and H4 – the canonical histones – and the DNA wrapped around the eight histones. Histones are small positively charged proteins and the negatively charged DNA binds to it. Changes of the chromatin structure through epigenetic mechanisms involve changes in the nucleosomes making the DNA more or less tightly bound to histone proteins, e.g. by adding distinct post-translational histone modifications.
Histone modifications: Are they the cause or the consequence of transcription?
In a recent review published in Nature Reviews Genetics, Adam Burton from the Institute for Epigenetics and Stem Cells, Robert Schneider from the Institute of Functional Epigenetics, and their colleagues Gonzalo Millán-Zambrano and Andrew J. Bannister put histone modifications and their cause and consequence on center stage: Are they really acting only mechanistically? Or is it time to consider histone PTMs as active components of a regulatory network?
To address these questions, the authors explore how DNA-templated processes, in particular transcription, affect, regulate, and are interdependent on histone PTMs.
Millán-Zambrano et al. (2022). Histone post-translational modifications — cause and consequence of genome function. Nat Rev Gen.