Nearly all of your cells contain an  identical copy of your entire genetic code:   the full cookbook for how to make every kind  of protein that your cells are capable of.

And that’s true for many other forms of complex  life as well, including plants and many fungi. The cells in your stomach have all the same  instructions as the cells in your heart.

I feel like there’s a good joke in  there about the way to a person’s   heart being through their stomach  but it’s just not translating. Like the joke ribosomes in my  brain must be hitting a stop codon. Anyway, don’t worry: your stomach isn’t going to  start beating in the same rhythms as your heart.

Despite having the same information,   those stomach cells ignore the instructions  they don’t need, in the same way that I might   ignore all the recipes in a cookbook that  contain jalapenos, because heartburn, ugh! In the words of the old African-American  proverb: “Ain’t nobody got time for that”! Anyway, cells pull off this spectacular feat  by regulating the way that genes get expressed.

Hi! I’m Dr. Sammy, your friendly neighborhood  entomologist, and this is Crash Course Biology.

Now where did I put that recipe for  the world’s greatest theme music… [THEME MUSIC]

Our cells are amazing. Now, I know what you’re  probably thinking, “Dr. Sammy,   you say that about all the biology stuff.”  Well, yeah, but that’s because it’s true!

In order to do the jobs that they need to do,   our cells can selectively use certain  genes while /ignoring/ others. It’s called gene regulation, and  it’s the process that determines   which proteins get made, and  when and where they’re created. And proteins are important in  just about everything we do.

Like, are you binge-watching  more Crash Course after this? Eating a plate of spaghetti? Taking your pet coconut crab out for a walk?

It’s all thanks to your cells making proteins. To make a protein, cells start with a section  of DNA called a gene, and then, the information   in that gene gets copied, or transcribed,  into a piece of messenger RNA, or mRNA. Then, structures called ribosomes translate,  or read that mRNA, using it as the instructions   to make a chain of amino acids that  eventually fold up into a protein.

Okay, so that’s the TLDR, but there’s much  more on how proteins get made in episode 35. For today, we’re talking about how that  process can be interrupted at nearly any stage. You see, our cells have access  to about 20 thousand genes.

That’s a whole grocery  store’s worth of ingredients. But like any good chef, our  cells know which ones to use. They don’t have to express every  gene in their DNA to make a protein.

For instance, there are certain genes in nearly   all of your cells that are  only expressed in your heart. They allow for the creation of proteins  that help your heart muscles – and only   your heart muscles – contract in  that special heartbeat rhythm. And those same heart cells  contain genes that only get   expressed in your stomach, helping it digest food.

This variation in how different kinds  of cells express themselves based on   their unique function is called  differential gene expression. And much like how a chef might need to  adjust a menu based on the season or   available ingredients, our cells  have to regulate gene expression   based on factors like temperature  or availability of nutrients. All of this can affect which proteins a cell needs  and, by extension, which genes get expressed.

So gene expression can change from year to  year, day to day, or even minute to minute. This allows cells to adapt as  the world changes around them. Like, when you get hungry, thirsty,  or even when you fall asleep.

There are a lot of ways that gene  expression can be changed and regulated. In fact, there are too many for us  to fully explain in the episode,   but we’ve picked some highlights. One of the main ways that differential gene expression happens is through  transcriptional regulation.

That means it regulates the  way DNA is copied into mRNA. You see, our DNA is expansive, but  less than two percent of the roughly   three billion letters actually code for proteins. The rest of it… well, for a long time,  scientists didn’t know what the rest of it did.

They called it “junk DNA”. But with more research, we’ve learned  that a lot of this non-coding DNA,   as it’s now called, is involved  in turning genes on or off. Normally, to kickstart transcription  and create a piece of mRNA,   a protein called a transcription  factor has to bind to a section   of DNA called a control element -  a short snippet of non-coding DNA.

That then tells cells whether or not  to begin the protein-making process. Some combinations of control elements  tells cells to begin transcription. While others, appropriately called  silencers, act like a stop sign.

When transcription factors bind to  silencers, transcription is blocked. No mRNA, no gene expression. But, even if an mRNA molecule is produced, that  doesn’t mean it’ll necessarily be expressed.

For instance, mRNA can get spliced before  it has a chance to get translated, or read. This creates different proteins  from the same original molecule. Let’s say an mRNA has sections 1 through 5.

It can be sliced and diced so that the message  only codes for a protein with sections 1,   3, and 5 — or just 2, 3, and 4,  depending on what the cell needs. Or, the mRNA can have a run-in with that  stuff that they used to call junk DNA. Turns out a lot of it gets transcribed  into little sections of RNA,   like microRNA or small interfering RNA.

And those sections don’t get translated  into proteins because they have another job. They bind to mRNA that was  on its way to get translated,   and break it down before translation happens. And it makes a difference how long mRNA floats  around in a cell before it’s broken down.

Think about it: if it takes a long  time for an mRNA to break down,   it’ll be translated into more and more  copies of a protein in the meantime. Now, none of what we’ve just talked about so far  is passed on when a cell divides into new cells. Each new cell does its own regulation based  on signals it gets from its surroundings.

But there is one category of gene  regulation that is heritable,   meaning it can be passed on to new cells,  and if it happens in a sperm or egg cell,   then it can even be passed on to  an organism’s offspring’s cells. These are called epigenetic mechanisms,  which are heritable modifications to   gene expression that don’t directly  change the underlying DNA sequence. Instead of changing the sequence of DNA,   epigenetic mechanisms modify what part  of the DNA is accessible for translation.

And there are a couple of different ways  to alter gene expression epigenetically. One involves the way DNA gets packaged. See, DNA isn’t floating around  the nucleus all willy-nilly.

That would be like trying to stuff your  entire wardrobe into your carry-on bag. Some organisms have literally meters of  DNA in each cell, and unless it’s wound up   into a compact package, those cellular  bags are going to burst at the seams. So, cells keep all this DNA organized  with the help of proteins called histones.

They’re like structural beads that DNA  wraps around to stay nice and neat. And when it comes to gene expression,  how these histones are arranged can   also determine whether or  not a gene gets turned on. Histone modification works by essentially  exposing certain genes for transcription   and hiding others so they can’t be copied or read.

Cells can also change expression  epigenetically by tagging genes   with particular molecules in a  process called DNA methylation. This typically can’t turn genes on, but it  can turn them off in a couple different ways. For example, the molecules can tell  histones to condense and hide certain genes.

Or, they can block transcription  factors from binding. Either way, this halts the  process before mRNA is produced. These epigenetic mechanisms  play a big role in our lives.

Someone’s environment and even their levels of  stress can affect how their DNA is methylated,   how their bodies behave, and might  even get passed on to their children. Doctors have known for years that  experiencing persistent discrimination   causes forms of stress that are  linked to different health risks. But more recent studies have found links  between that discrimination and DNA methylation.

This suggests that stress driven by societal   inequities could be causing  physical changes in DNA. And although it’s too early to say for sure,   they’re even beginning to find evidence  that these changes may be able to pass   from parent to child — even if the child never  experiences the same discrimination themselves. But, there is some hope to be had here.

Understanding the damage these stressors cause  can help researchers, activists, and community   leaders work toward removing those stressors at  the source, and better address their impacts. Now, that doesn’t mean that all  epigenetic modifications are bad. In fact, many are essential to proper functioning.

Like, male mammals typically  have an X and a Y chromosome,   while female mammals typically have two X’s. But expressing two of the same chromosomes  could potentially cause a lot of issues. So, one of the chromosomes in female  mammals is epigenetically silenced,   remaining in a stable, inactive state.

That means mammals of all sexes  express a single X chromosome. Like I said, your cells have lots of  ways of regulating gene expression. These are just a few of the many amazing  tricks that your cells have up their sleeves.

Er, membranes. You’ve got transcriptional regulation,   including epigenetic ways to guide transcription  and non-epigenetic ways like control elements. All of that is just very fancy lingo that really   means “if the cell doesn’t make  mRNA, it can’t build a protein.” You’ve also got post-transcriptional processes  that regulate translation from mRNA to protein.

These include alternative mRNA splicing,  interfering mRNAs, and much more. So at every level of gene expression,   your cells have ways to regulate whether  or not they really need that protein. It’s basically a long sequence of repeatedly  asking, “Are you sure about that?” The ability to regulate gene expression  is what allows organisms to be so diverse,   and complex, and interesting!

It makes your stomach muscles distinct from your   heart muscles, and it allows your cells to  respond as conditions change around them. But if we’ve learned anything in this episode,   it’s that genes don’t get  turned on or off in a vacuum. Someone’s environment and even how  they’re treated may play a role in   how DNA gets methylated —  sometimes, for the worse.

Still, if stress can alter gene expression and  make someone more likely to develop a disease,   that also means a life /without/ those  stressors could prevent those changes. In other words, making a more just,   equitable world could lead to changes that  run deep — all the way down to someone’s DNA. In our next episode, we’re going to spend some   time talking about how mutations can  emerge in our bodies’ genetic codes.

Peace! This series was produced in  collaboration with HHMI BioInteractive. If you’re an educator, visit  BioInteractive.org/CrashCourse for   classroom resources and professional development  related to the topics covered in this course.

Thanks for watching this episode of Crash  Course Biology which was filmed at our studio   in Indianapolis, Indiana, and was made  with the help of all these nice people. If you want to help keep Crash  Course free for everyone,   forever, you can join our community on Patreon.