The role of 3D chromatin architecture in regulation of gene expression and cell identity

Regulation of gene expression: Multiple layers of complexity

Signal Transduction


Transcription Factors

and Co-factors

DNA Methylation

Chromatin Modifications

and Histone Variants

Subnuclear Localization

and Long-Range




Somatic Cell Reprogramming​

Model for Nanog's interactome changes
during reprogramming

Somatic cell reprogramming is the process by which enforced expression of defined embryonic transcription factors (TFs) in somatic cells changes their fate to induced pluripotent stem cells (iPSCs). The latter cells -similar to embryonic stem cells (ESCs) derived by explanting early mammalian embryos- are characterized by two hallmark properties: they can self-renew infinitely in culture and they can differentiate to form all cell types of the adult body holding a great potential for regenerative medicine. In addition, iPSC technology offers a unique and tractable experimental system to study the molecular mechanisms underlying cell fate changes. In our lab we focus on the study of three-dimensional chromatin architecture and its dynamic rearrangements upon differentiation and reprogramming. We hypothesize that the interplay among transcription factors, epigenetic modulators and chromatin topology determines the gene expression program and cell identity. Unraveling the principles of this interplay will enable deeper understanding of physiological or pathological cell fate alterations, such as lineage specification and cancer respectively.



We use high-throughput sequencing techniques such as 4C-Seq, Hi-C, HiChIP, ChIP-seq and scRNA-seq. We also employ biochemical, molecular, and cell biology assays, as well as novel mouse genetics tools. Our data on chromatin organization, combined with gene expression data, DNA methylation and chromatin occupancy studies, will provide an integrative view of epigenetic regulatory mechanisms, which govern pluripotency, differentiation, and reprogramming.


    Genomic distribution of Nanog-interacting regions



Aim 3

Role of pluripotency factors and cofactors in establishment and maintenance of interactions

Aim 1

Regulation of imprinted gene expression.

The paradigm of Dlk1-Dio3

Aim 2

Coregulation of lineage-related genes during differentiation/ Discovery of novel regulatory elements



© 2016 Apostolou Lab @ Weill Cornell Medical College