LSD1 is the first described histone demethylase which demethylates
H3K4me1/2 (Shi et el., 2004), thus, causing transcriptional repression.
Alternatively, LSD1 was demonstrated to have H3K9me1/2 demethylase activity
when bound by androgen receptor, hence, causing transcriptional activation
(Schule et al., 2005). LSD1 is commonly recruited by the so called CoREST core
complex including: RCOR1, HDAC1 and HDAC2 among others and therefore is
coupled with histone deacetylation and transcriptional repression (Foster et al.,
2010). It is an important regulator of pluripotency in early development and it
occupies, along with pluripotency factors NANOG and OCT4, the promoters of
major lineage determining genes that are poised for activation in the pluripotent
state, (Adamo et al., 2011). There are four described isoforms for LSD1: LSD1,
LSD1-E2a, LSD1-8a and LSD1-E2a/E8a (Zibetti et al., 2010). While the Cterminus
of LSD1 is extensively studied and the function of the isoforms LSD1-E8a
and LSD1-E8aE2a is described, there is scarce knowledge on LSD1 N-terminus
unstructured region and the SWIRM domain. In this project I examined the role of
the differently spliced exon 2a on the function of the SWIRM domain through
generation of eight constructs coding for the N-terminal portion of LSD1 SV1 and
SV2 fused with a C- or N-terminus FLAG tag. I then performed an
immunoprecipitation experiment followed by mass spectrometry and proteomics
analysis that led to the identification of previously unknown binding partners to the
LSD1 SWIRM domain: NONO and IGF2B3.
| Identifer | oai:union.ndltd.org:kaust.edu.sa/oai:repository.kaust.edu.sa:10754/630229 |
| Date | 11 1900 |
| Creators | Fadaili, Yara |
| Contributors | Adamo, Antonio, Biological and Environmental Sciences and Engineering (BESE) Division, Hamdan, Samir, Aranda, Manuel |
| Source Sets | King Abdullah University of Science and Technology |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Rights | 2019-12-09, At the time of archiving, the student author of this thesis opted to temporarily restrict access to it. The full text of this thesis became available to the public after the expiration of the embargo on 2019-12-09. |
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