The BCL7A gene holds the instructions for producing the BCL7A protein, a molecule involved in managing how genetic information is accessed and used. The processes influenced by BCL7A are foundational to the normal function of cells. Its involvement in these cellular activities has made it a subject of considerable interest in biology and medicine, as scientists work to understand its precise roles in both health and disease.
Unveiling BCL7A: Discovery and Genetic Profile
The BCL7A gene was first identified through research into the genetic underpinnings of certain cancers. Its name, B-cell CLL/lymphoma 7A, originates from its discovery in a Burkitt lymphoma cell line. It was found to be involved in a complex chromosomal rearrangement, known as a three-way translocation, that also involved the MYC and IGH genes, pointing to its potential role in high-grade B-cell non-Hodgkin lymphomas.
The BCL7A gene is located on human chromosome 12 at position 12q24.31 and directs the production of a protein composed of 231 amino acids. This protein is part of a small family that includes BCL7B and BCL7C, which share sequence similarity but do not appear to have overlapping functions during development. The BCL7A protein is expressed at low levels in a wide variety of normal tissues, suggesting a broad role in cellular maintenance.
BCL7A’s Role within the Cell
The primary function of the BCL7A protein is as a component of the SWI/SNF chromatin remodeling complex, also known as BAF. This complex plays a part in regulating gene expression. Inside the cell’s nucleus, DNA is tightly wound around proteins called histones, forming a condensed structure known as chromatin, which makes much of the genetic code inaccessible.
For a gene to be read and its instructions used, the section of DNA containing that gene must be unwound. Using energy, the SWI/SNF complex can slide, evict, or restructure histone arrangements, thereby altering chromatin structure. This remodeling process makes specific genes accessible to the cellular machinery for transcription, effectively turning them on or off.
Within this complex machinery, BCL7A is a core subunit of the ATPase module. Its presence helps to stimulate the activity of the complex’s motor, an ATPase enzyme like BRG1. This enhances its ability to bind to DNA and reposition nucleosomes efficiently, helping to control which genes are active at any given time.
BCL7A and Human Development
The regulatory function of BCL7A is important during human development. As an organism grows, cells must differentiate into specialized types, like neurons and skin cells. This requires precise, coordinated changes in gene expression, and the BCL7A-containing SWI/SNF complex helps orchestrate these genetic programs.
BCL7A is highly expressed in neural progenitor cells (NPCs) and mature neurons, where it supports neurogenesis, the process of generating new neurons. It helps modulate signaling pathways like Notch and Wnt, which influence whether a progenitor cell becomes a neuron or a different type of brain cell. The gene also appears to influence mitochondrial bioenergetics, the processes by which cells generate energy for neural differentiation.
The absence of functional BCL7A during development can have significant consequences. Mouse models show that a complete lack of the Bcl7a gene is lethal around the time of birth. When the gene is removed only in postmitotic neurons, it leads to motor coordination problems and affects the structural development of brain cells, like the dendritic branching of Purkinje cells in the cerebellum.
When BCL7A Goes Awry: Implications in Disease
Disruptions to the BCL7A gene or the protein it produces are linked to several human diseases, most notably cancer. Because of its role in regulating gene expression, BCL7A is categorized as a tumor suppressor. Its proper function helps maintain normal cell growth, and its inactivation through mutations or deletions can contribute to uncontrolled proliferation.
In hematological malignancies, such as diffuse large B-cell lymphoma (DLBCL), mutations and loss of BCL7A are frequently observed. Specific mutations can produce a truncated, non-functional protein that cannot properly integrate into the SWI/SNF complex. This impairment disrupts the complex’s tumor-suppressive activities, and low expression of BCL7A is also associated with poorer outcomes in solid tumors like glioma.
Beyond cancer, malfunctions in SWI/SNF complex components are connected to neurodevelopmental disorders. Given BCL7A’s specific roles in neuronal development, disruptions in its function could contribute to conditions involving cognitive or behavioral abnormalities.