Functions of the enzyme CBP in embryo development
A study published in Molecular Cell reveals that both CBP’s presence and its enzymatic function are essential for proper gene activation at the start of development. Disruptions in this process lead to severe developmental defects, the study shows.
When an embryo develops into different types of cells such as skin, nerve or muscle, each of its cells carries the same genetic information. Yet, different cell types must activate only the specific genes they need while keeping others silent. Whether a gene is active or not is influenced by an epigenetic code, marking the genes that should be used in each cell type. One such epigenetic mark is deposited by the enzyme CBP. This protein is present in all animals, from flies to humans, yet the exact mechanism of its action has remained unclear.
In the study, the researchers used a classic model organism, the fruit fly Drosophila melanogaster, to uncover the role of CBP during the earliest stages of development. In this process, the dormant genome in the embryo must be fully activated for the first time.
Synonymous with a factory
“To illustrate this process, imagine a factory at the break of dawn. The machines – representing genes – are silent. Workers, RNA polymerases responsible for making different messenger RNAs (mRNAs) from the genes, arrive and begin assembling the production lines. The mRNA then gets translated into a protein, each with a specific function—like the product of a factory line”, says Sergei Pirogov, researcher at Department of Molecular Biosciences, The Wenner-Gren Institute at Stockholm University.
“Just like a factory must operate in a coordinated manner, gene activation in the nucleus must be tightly controlled to ensure proper development. A class of proteins called transcription factors are like line supervisors, ensuring each section of the factory is ready. But the machines won’t start until the chief engineer, CBP, gives the green light”.
CBP has dual roles
“We have shown that CBP acts in two steps. First, as an enzyme, it performs a chemical modification known as histone acetylation, which "licenses" genes for activity by giving RNA polymerase the permission to start transcription. But second, CBP plays a more hidden role: it supports the transcription factors in bringing in RNA polymerases in the first place”, says Mattias Mannervik who led the study together with researchers from the University of Wisconsin-Madison, USA.
To understand these dual roles, the researchers designed experiments that either completely removed CBP or disabled only its enzymatic activity. Without CBP at all, it can no longer assist the transcription factors, and the whole process stalls – even the very first step of gene transcription, initiation, fails. But when the researchers specifically disable only the enzymatic function of CBP, removing its ability to "approve" transcription, the RNA polymerase machinery assembles but cannot proceed. The factory is set up, but the lines run idle. This stalled state is known as promoter-proximal pausing.
“Our findings show that both CBP’s presence and its enzymatic function are essential for proper gene activation at the start of development. Disruptions in this process lead to severe developmental defects. This is especially important because CBP dysfunction in humans is known to cause Rubinstein-Taybi syndrome, a condition marked by developmental delays and physical abnormalities”, says Sergei Pirogov.
By shedding light on how CBP coordinates gene activation, the researchers hope to better understand not just normal development, but also how its breakdown contributes to disease.
Read the study in Molecular Cell:
Last updated: June 3, 2025
Source: Communications Office