Part 1: Introduction & the Epigenome

In this 3 part installment series on Epigenetics, we’ll explore the Epigenome, Regulatory Mechanisms and Developmental Impact.  At the conclusion of each installment, we’ll then speculate on Transgender implications.


From the Greek, epi is a loanword prefix meaning “upon,” “on,” “over,” “near,” “at,” “before,” “after,” used to form new compound words.  Genetics is the biological scientific study of heredity, and organisms resemblances and differences as resultant interactions with their genes and environment.  Ergo, Epigenetics is the branch of genetics focusing on the chemical changes happening above the DNA sequence.

In April 1953, James D. Watson and Francis Crick published the article, “Molecular structure of nucleic acids: A structure for deoxyribose nucleic acid” in Nature.  Having discovered the double helix that is DNA, this “golden key” opened the means for further research in Biology and on to the field of Genetics and the mapping of the Human Genome.  Fast forward 50 years, to 2003 and the final notes on what is now known as the Human Genome Project, was completed.  This international collaborative exploration mapped all the genes of homo sapiens.  Welcome now to present day genetics, currently in its pilot stages, is HEP, the HEPHuman Epigenome Project, a public/private consortium to map out the MVPs, Methylation Variable Positions, in the Human Genome.


What is the Epigenome?

The over 3 billion base pairs that comprise the Human Genome are the Nucleotide building blocks that make up all human life on Earth.  These genes need instructions on what to do, how to behave and how to function.  The Epigenome “marks” the Genome with Genetic Markers, or tags, which modulate genes by either activating or inactivating them.  These protein modifications are dynamic in nature, meaning they can impact development at any point in a person’s lifetime and can vary in time duration.  Epigenome chemical compounds are not part of the DNA sequence, they are attached to the strand, and do not alter the DNA code.

What is Epigenetics?slide_1-elipse

The relatively recent and polemical field of epigenetic biology focuses on the heritable changes in gene expression, without modifying the underlying DNA sequence.  Genetic change happens as genes are turned on and off, called Gene Expression.

An epigenetic change is influenced by many factors, including, lifestyle, environment, health factors, age, culture, experiences, thoughts and actions.  Epigenetic markers on genes are transmitted throughout a bloodline, giving rise to epigenetic coding for future generations.  These external influences give pause to the Nature vs. Nurture debate.  No longer can either philosophy be argued as an independent cause for human development.

If we visualize this multi-generational process as a chalk board, each time a code is written, it is also re-written with each succeeding generation.  Though, not entirely.  Certain markers are retained, akin to chalk residue when the board is erased.  These epigenetic “after images” are passed along, as are new gene markers summarily added, as the aforementioned interactive factors affect development.

think of the epigenome as a complex software code

It is known that the brain develops separate and apart from the genital development.  Given that epigenetic coding is malleable and is affected by myriad factors, it is reasonable to extrapolate that binding proteins on the brain areas affecting gender identity can get confused during fetal development.  As the child grows, prenatal and postnatal, these instructions are activated and discordant signals are released.


Epigenetic’s has long been thought of as a key development aspect of sexual differentiation.  Chromatin is being focused in on as the causation of long term gene expression changes.  Inclusive of development only, Chromatin may also be the mechanism responsible for gender identity.  By studying identical twins, like the Maineses, where one twin identifies as transgender, genetic differences can be identified.  However, conclusively identifying what makes one person transgender may be decades away, if ever realized.


Epigenetic Process

These changes are of a phenotype and not a genotype of change.  Such epigenetic modifications can differentiate the programming of a skin cell, heart cell, brain cell, or gland cell, et cetera.  A 2006 Discover article suggests that we “think of the epigenome as a complex software code, capable of inducing the DNA hardware to manufacture an impressive variety of proteins, cell types, and individuals.”  These modifications are also present in individual cells of a given organ.  It can be surmised than, that epigenetics is responsible for maintaining the health of organs while also regulating the aging process.  We will explore the regulatory processes in the next article.

Speculation: What Does This Mean For Transgender Individuals

If feelings and actions and thoughts can play a role on the development of the epigenome, hence altering the DNA coded instructions, are then we also individually responsible for the “transgender brain?”  Supporting data would revolve around the median age ~5 years, when transgender individuals cite the earliest recollection of when they felt different.  If this is accepted as a general rule, what factors occur in our youth that affected our epigenetic gender identity?

If such external influences are found to modify gene expression, through generations, then some distant relative can be the zero-factor for our being transgender.  Given genes are switched on and off at various times in one’s lifetime, this is at least a contributing factor for consideration.


We would love to hear your comments @TransgenderU #epigenetics.

mir, irini, peace, amn,