Skip to main content
Loading Events

« All Events

  • This event has passed.

SEMINAR: Research in Progress (Zachary Carico, PhD and Onur Oztas, PhD) UNC-CH

May 8, 2018 @ 11:00 am - 12:00 pm

Zachary Carico, PhD
Postdoctoral Researcher
Dowen Lab

Abstract: Proper transcriptional regulation requires the precise targeting of enhancer activity to certain genes and not other genes. In the mammalian genome, chromatin loops contain enhancers and their target genes, and serve to protect adjacent non-target genes. Formation of these chromatin loops, termed insulated neighborhoods, is driven by binding of the zinc-finger protein CTCF and the Cohesin complex to intergenic sites flanking genes and their enhancer elements. Here, we explore molecular mechanisms through which the Cohesin complex locates the boundaries of insulated neighborhoods and directs loop formation. In particular, we investigate the role of the Cohesin subunit STAG2, a tumor suppressor, in regulating insulated neighborhood formation and function. We used CRISPR/Cas9 genome editing to generate murine embryonic stem (mES) cell lines that lack expression of STAG2, and found that STAG2-null mES lines showed a striking reduction in transcriptional insulation across several insulated neighborhood boundaries, including at the loop domain in which the OCT4 pluripotency master regulator is encoded. The mES gene expression program was consequently disrupted, as shown by reduced expression of mES identity genes and premature expression of transcripts associated with ectodermal and endodermal lineage specification. We are currently investigating how loss of STAG2 regulates Cohesin complex chromatin localization and loop formation in order to maintain transcriptional insulation globally.

Onur Oztas, PhD
Postdoctoral Research Associate
Sancar Lab

Abstract: Plants possess a circadian clock that regulates physiological and developmental processes with daily environmental changes. Throughout the day, plants are exposed to various DNA damage-inducing stresses, such as ultraviolet (UV) radiation from sunlight. To maintain their genome integrity, and their fitness, plants eliminate UV-induced DNA lesions by nucleotide excision repair, which detects bulky DNA damage, and removes the damage-containing oligomers by properly concerted dual (5’ and 3’) incision, followed by gap filling and ligation. Excision repair can be stimulated by either the direct recognition of DNA lesions by the repair factors, called global repair, or by the DNA damage-blocked transcription, named transcription-coupled repair. In Arabidopsis, most of the excision repair proteins in yeast and mammals are well-conserved; however, this species lacks an evident XPA protein and has some excision repair factor genes duplicated, suggesting that excision repair in Arabidopsis might exhibit unique features. In our study, we generated the genome-wide map of nucleotide excision repair at a single-nucleotide resolution, and monitored the circadian dynamics of this repair in Arabidopsis thaliana. We found that transcription-coupled repair plays the dominant role in correcting the damage sites along the genome, which is also influenced by the chromatin state. We further identified that nucleotide excision repair exhibits a circadian oscillation due to the daily rhythms of transcription-coupled repair.


May 8, 2018
11:00 am - 12:00 pm
Event Tags:
, , ,