Education & Training
- B.S., Molecular Biology and Biochemistry, University of Pittsburgh-2007
- Ph.D., Molecular, Cell and Developmental Biology, University of Pittsburgh-2012
- Postdoc, Molecular, Cell and Cancer Biology, University of Massachusetts Medical School- 2012-2017
Research Interest Summary
Embryonic stem (ES) cells are of considerable biomedical interest because of their following two properties: the unlimited capacity to proliferate without accumulation of genetic or epigenetic alterations that alter their identity (self-renewal) and the ability to differentiate into any of the approximately two hundred different cell types found in the adult organism (pluripotency). Because of these properties, ES cells are excellent candidates for the development of new therapies for degenerative diseases. However, while therapeutic trials with ES cell-derived tissue-specific cells have begun, a major obstacle in the development of stem cell-based therapies is the inability to robustly differentiate ES cells into homogeneous populations of committed progenitors. On one hand, it is not currently possible to obtain large amounts of most cell types from differentiating ES cells. On the other hand, if undifferentiated ES cells remain within the population of cells transplanted into a patient, tumors may arise from this population. Therefore, a more comprehensive understanding of the factors regulating ES cell self-renewal and differentiation pathways should aid the design of more robust differentiation protocols that facilitate the development of ES cell-based therapies.
An unexpected finding from genome-scale studies is that the majority of the human genome is transcribed. Although protein-coding regions comprise only ~2% of the human genome, at least 75% is transcribed at detectable levels. These findings have led to a re-evaluation of the mammalian genome – if non-coding regions are transcribed, the resulting non-coding RNAs (ncRNAs) may have important functions. This possibility has tremendous ramifications for biomedical research, since clinical samples subjected to diagnostic sequencing are typically examined at only a subset of important genes, and only in their coding sequences.
One key regulatory mechanism shared among eukaryotes is the control of access to regulatory sequences by transcription factors through alteration of nucleosome occupancy or positioning. Nucleosome remodeling factors use the energy from ATP hydrolysis to reposition, deposit, or remove nucleosomes at regulatory regions by altering histone-DNA contacts. The actions of nucleosome remodeling factors are critical for transcription, DNA repair, and other essential cellular functions. Given their key roles in regulation of gene expression and genome integrity, it is perhaps not surprising that nucleosome remodeling factors are among the most commonly mutated or epigenetically silenced genes in human cancers and neurological disorders. However, the mechanisms by which loss of nucleosome remodeling factors function contributes to cancer and disease development are largely unknown.
Our lab will address a number outstanding questions regarding transcription regulation in murine ES cells and human cancer cells.
SJ Hainer*, A Boskovic, KN McCannell, OJ Rando, and TG Fazzio*. Profiling of Pluripotency Factors in Single Cells and Early Embryos. Cell. 2019 April 2 pii: S0092-8674(19)30276-4
SJ Hainer* and TG Fazzio*. High-Resolution Chromatin Profiling Using CUT&RUN. Current Protocols in Molecular Biology. 2019 Jan 28:e85.
D Acharya, SJ Hainer, Y Yoon, F Wang, I Bach, JA Rivera-Perez, TG Fazzio. KAT-independent gene regulation by Tip60 promotes ESC self-renewal but not pluripotency. Cell Reports. 2017 19: 671-679.
SJ Hainer, KN McCannell, J Yu, L Ee, LJ Zhu, OJ Rando, TG Fazzio. DNA methylation directs genomic localization of Mbd2 and Mbd3 in ES cells. eLIFE. 2016 Nov 16;5.
SJ Hainer and JA Martens. Regulation of chaperone binding and nucleosome dynamics by key residues within the globular domain of histone H3. Epigenetics & Chromatin. 2016 Apr 30;9:17.
SJ Hainer and TG Fazzio. Regulation of Nucleosome Architecture and Factor Binding Revealed by Nuclease Footprinting of the ESC Genome. Cell Reports. 2015 Oct 6;13(1):61-9
SJ Hainer, W Gu, BR Carone, BL Landry, OJ Rando, CC Mello, TG Fazzio. Suppression of pervasive noncoding transcription in embryonic stem cells by esBAF. Genes & Development. 2015 Feb 15;29(4): 362-378
PB Chen, LJ Zhu, SJ Hainer, KN McCannell, TG Fazzio. Unbiased chromatin accessibility profiling by RED-seq uncovers unique features of nucleosome variants in vivo. BMC Genomics. 2014 15:1104.
BR Carone, JH Hung, SJ Hainer, MT Chou, DM Carone, Z Weng, TG Fazzio, OJ Rando. High-resolution mapping of chromatin packaging in mouse embryonic stem cells and sperm. Developmental Cell. 2014 Jul 14:11-22
SJ Hainer, JA Pruneski, RD Mitchell, R Monteverde, JA Martens. Intergenic transcription causes repression by directing nucleosome assembly. Genes & Development. 2011 Jan 1;25(1):29-40.