Hi Alejandro,
Let’s start by discussing the meaning of “cis” and “trans.” The term cis is derived from the Latin root “cis,” meaning “the same side as.” In contrast, the term trans comes from the Latin root “trans,” meaning “across from.” In molecular biology, a cis-acting (or cis-regulatory) element refers to a region of the chromosomal DNA that regulates the transcription or expression of a gene that is on the same chromosome. A trans-acting (or trans-regulatory) element, on the other hand, refers to a soluble protein that binds to the cis-acting element of a gene to control its expression. The gene that encodes the soluble trans-acting protein can reside on any chromosome, often located far away from the gene whose expression it regulates.

Cis-acting elements are not part of the coding sequences of the gene they regulate: they may be near the promoter or the 5’ region of the gene, and in some cases they may be many kilobases downstream of the gene. In eukaryotes, enhancers are a common type of cis-acting element. As its name implies, an enhancer promotes gene expression when the appropriate trans-acting element(s) binds to it.

Trans-acting elements, also known as transcription factors, can either promote or inhibit gene expression. A given transcription factor can work with other transcription factors to regulate the expression of a single gene or a group of related genes. Conversely, a gene may have several transcription factors bind to its cis-regulatory elements at the same time or at different times, depending on the cellular and environmental signals. As you might imagine, these different levels of gene regulation give the organism a wide range of mechanisms to control which genes are turned on or off at any given moment.

As you can see, cis- and trans-acting elements are key players when it comes to gene regulation!

Follow these links to review the definitions of cis- and trans-regulatory elements:

http://www.nature.com/scitable/definition/cis-regulatory-element-cis-regulatory-element-75

http://www.nature.com/scitable/definition/enhancer-163

http://www.nature.com/scitable/definition/transcription-factor-general-transcription-factor-167

http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=mcb&part=A7315#A7406

http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=mcb&part=A7315&rendertype=def-item&id=A7834

For more in-depth information to help you learn about gene regulation and transcription factors, follow these links:

http://www.nature.com/scitable/topicpage/some-sections-of-dna-do-not-determine-6525008

http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=eurekah&part=A67432#A67433

http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=mcb&part=A2536#A2540

http://www.nature.com/scitable/topic/gene-expression-and-regulation-15

To visualize what cis-acting elements look like in the context of a gene, follow these links:

http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=mcb&part=A2558#A2566

http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=mcb&part=A2558&rendertype=figure&id=A2567

Welcome back Umesh,
As you likely know, mitochondria are cellular organelles found in eukaryotic organisms that serve as cellular powerhouses. Before we jump in and answer your question, let’s briefly discuss the anatomy of mitochondria. Mitochondria are double-membrane organelles. From the outside in, mitochondria consist of an outer membrane, an intermembrane space, an inner membrane, and a matrix. Mitochondria harbor multiple copies of their circular genome within their matrix. Although they come complete with their own genome, mitochondria are not entirely self-sufficient: they also rely on nuclear-encoded genes to produce cellular energy.

Why do mitochondria have their own genome? Where did it come from? After mitochondrial genomes were discovered in the early 1900s, researchers first hypothesized that mitochondria were likely evolutionary descendents from endosymbiotic bacteria. Endosymbionts are organisms that live within the body or cells of another organism. Today, this widely regarded theory is called endosymbiosis. Now that we know the sequences of mitochondrial and nuclear genomes from a wide range of organisms, scientists have confirmed that mitochondria are indeed the likely descendents of endosymbiotic bacteria, which are believed to have merged with eukaryotic cells around two billion years ago. Like today’s mitochondria, the endosymbiotic bacteria originally harbored a circular DNA genome.

Why did endosymbiosis occur? During that time, life on Earth was exclusively unicellular, and it is believed that aerobically respiring bacteria were engulfed by anaerobic eukaryotes. Over time, the conditions on Earth changed slowly. One major change believed to have driven the rapid expansion of eukaryotes was the increase in the relative amount of atmospheric oxygen. This resulted in a need for eukaryotes to develop and maintain cellular mechanisms to cope with higher oxygen levels. Aerobic respiration from endosymbiotic bacteria provided eukaryotes with the ability to adapt to these new conditions.

Over time, many of the genes from the bacterial endosymbionts were transferred to the eukaryotic nucleus. The mitochondrial organelle, however, retained a circular DNA genome encoding mitochondria-specific factors required for cellular aerobic respiration. Indeed, when comparing genome sequences of prokaryotes to eukaryotic mitochondrial genome sequences, a great deal of conservation can be found between bacterial genes encoding proteins involved in aerobic respiration and genes involved in mitochondrial respiration.

Now, let’s end with a discussion of some interesting trivia related to mitochondria. Thanks to genes encoded by the mitochondrial genome, mitochondria build their own ribosomes, which are much more similar to bacterial ribosomes than to eukaryotic cytoplasmic ribosomes. Interestingly, this similarity leads to the sensitivity of eukaryotic cells to some antibiotics, which adversely affects bacterial ribosomes and mitochondrial ribosomes but not cytoplasmic ribosomes.

You might also be interested to read that humans always inherit their mitochondria from their mothers — together with multiple copies of their mother’s circular mitochondrial DNA genome! As a result, your mitochondrial DNA will be very similar to the mitochondrial DNA of your mother’s mother, but it will not be similar at all to the mitochondrial DNA of your father’s mother. Additionally, disease-associated mutations in the mitochondrial genome exhibit a characteristic maternal inheritance pattern.

Finally, mutations occur at a faster rate in mitochondrial DNA than in nuclear DNA. Because of its accelerated mutation rate, it turns out that mitochondrial DNA is a good yardstick by which to measure evolutionary relatedness!

For general information about the cell biology of mitochondria, check out these links:

http://www.nature.com/scitable/topicpage/mitochondria-14053590

http://www.nature.com/scitable/topicpage/the-origin-of-mitochondria-14232356

For more information regarding endosymbiosis and details about eukaryotic mitochondria, please check out these excellent articles and reviews:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1693097/?tool=pmcentrez

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC99014/?tool=pubmed

http://www.nature.com/scitable/content/The-organization-and-inheritance-of-the-mitochondria-154

Follow these links to learn more about mitochondrial diseases and inheritance:

http://www.nature.com/scitable/topicpage/mtdna-and-mitochondrial-diseases-903

http://www.nature.com/scitable/topicpage/non-nuclear-genes-and-their-inheritance-589

http://www.nature.com/scitable/topicpage/Somatic-Mosaicism-and-Chromosomal-Disorders-867

:D Thank you so much

Hello LaTrentis,
Let’s start by discussing some biochemical definitions related to heterodimers. Then, we’ll provide you with some real-life examples of heterodimers. In biochemistry, the term “dimer” refers to a complex formed by two macromolecules, like proteins or nucleic acids. The term “homodimer” is used to describe a complex formed between two identical molecules. In contrast, the term “heterodimer” is used to describe a complex formed when two different macromolecules bind to each other — usually non-covalently.

Now, let’s discuss an example. Receptor tyrosine kinases (RTKs) are a well-studied example of proteins that can form dimers (both heterodimers and homodimers). RTKs are a group of transmembrane receptors involved in a functionally diverse set of cell signaling pathways. RTKs contain an extracellular domain that binds to ligands (called cytokines) and an intracellular domain that has kinase activity. The process of RTK dimerization is crucial for proper receptor function: When cytokines bind to the extracellular domain of an individual RTK, it undergoes a conformational change that allows it to bind to an adjacent RTK. RTK dimerization leads to the rapid activation of the intracellular kinase domain and subsequent activation of the downstream signaling pathway.

Some other examples of macromolecules that form dimers include transcription factors, antibodies, and tubulin (the globular proteins used to build microtubules). As you can see, the process of dimerization — including both homodimerization and heterodimerization — is absolutely critical for numerous biological processes. Notably, defects in dimerization, such as those associated with protein misfolding, can lead to catastrophic events in cells. We hope our explanation has increased your understanding of heterodimerization. We encourage you to explore the links we’ve provided below to learn more about heterodimerization.

To learn more about protein structure, folding, and dimerization, follow these links:

http://www.nature.com/scitable/topicpage/protein-structure-14122136

http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=mboc4&part=A388#A425

http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=stryer&part=A344

http://rpi.edu/dept/bcbp/molbiochem/MBWeb/mb1/part2/protein.htm

To learn more about RTKs, check out these links:

http://www.nature.com/scitable/topicpage/rtk-14050230

http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=mcb&part=A5803

http://www.nature.com/scitable/topicpage/regulation-of-erbb-receptors-14458003

Follow these links to learn more about dimerization by transcription factors, antibodies, and tubulin:

http://www.nature.com/scitable/topicpage/transcription-factors-and-transcriptional-control-in-eukaryotic-1046

http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=mboc4&part=A4446

http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=mboc4&part=A2957#A2967

http://www.nature.com/scitable/topicpage/microtubules-and-filaments-14052932