Related Experiment Video

Updated: May 8, 2026

HOX Loci Focused CRISPR/sgRNA Library Screening Identifying Critical CTCF Boundaries
10:10

HOX Loci Focused CRISPR/sgRNA Library Screening Identifying Critical CTCF Boundaries

Published on: March 31, 2019

Symplekin, a polyadenylation factor, prevents MOZ and MLL activity on HOXA9 in hematopoietic cells

Anne Largeot1, Jérôme Paggetti2, Julien Broséus1

  • 1Inserm U866, Labex LipSTIC team, Faculté de Médecine, Université de Bourgogne, 21000 Dijon, France.

Biochimica Et Biophysica Acta
|September 3, 2013
PubMed

Insights

Symplekin, a protein involved in RNA processing, interacts with MOZ and MLL, key leukemia-associated proteins. This interaction influences HOXA9 gene expression, revealing Symplekin

Area of Science:

  • Molecular Biology
  • Hematopoiesis
  • Cancer Biology

Background:

  • MOZ and MLL are histone modifiers implicated in leukemia through chromosomal translocations.
  • MOZ and MLL cooperate to regulate HOXA9 gene expression in hematopoietic stem/progenitor cells.

Purpose of the Study:

  • To identify novel proteins interacting with MOZ to elucidate the MOZ-MLL complex's mechanism of action.
  • To investigate the functional role of Symplekin in the context of MOZ and MLL function.

Main Methods:

  • Mass spectrometry to identify MOZ-interacting proteins.
  • Co-immunoprecipitation and immunofluorescence to confirm Symplekin-MOZ-MLL interactions and localization.
  • Functional assays to assess the impact of Symplekin inhibition on HOXA9 expression and MOZ/MLL recruitment.

Main Results:

  • Symplekin was identified as a MOZ-interacting protein and confirmed to interact and co-localize with MOZ and MLL in hematopoietic cells.
  • Symplekin inhibition reduced HOXA9 protein levels without affecting Hoxa9 mRNA, suggesting post-transcriptional regulation.
  • Symplekin inhibition led to increased recruitment of MOZ and MLL to the HOXA9 promoter.

Conclusions:

  • Symplekin plays a crucial role in the transcriptional regulation network involving MOZ, MLL, and HOXA9.
  • Symplekin's function in polyadenylation machinery assembly is linked to its role in MOZ/MLL-mediated gene repression.
  • These findings uncover a novel regulatory mechanism in hematopoietic gene expression with implications for leukemia research.
Keywords:
AMLsBRPFC-terminal domain of the RNA-polymerase IICPSF100CTD-RNA-PolIIEAF6Esa1-associated factor 6 orthologHATHMTHOXHOXA9HSF1ING5MLLMOZMOZ/YBF2/SAS2/TIP60 homology domainMYSTPHDRUNX1Spi-1/PU.1SymplekinTranscription regulationacute myeloid leukemiasbromodomain and PHD finger-containing proteincleavage and polyadenylation specificity factor 100heat shock factor 1histone acetyltransferasehistone methyltransferasehomeoboxinhibitor of growth 5mixed lineage leukemiamonocytic leukemia zinc fingerplant homeodomainrunt-related transcription factor 1spleen focus forming virus proviral integration oncogene/purine-rich box-1

More Related Videos

Pooled shRNA Screen for Reactivation of MeCP2 on the Inactive X Chromosome11:15

Pooled shRNA Screen for Reactivation of MeCP2 on the Inactive X Chromosome

Published on: March 2, 2018

Toxicological Assays for Testing Effects of an Epigenetic Drug on Development, Fecundity and Survivorship of Malaria Mosquitoes10:26

Toxicological Assays for Testing Effects of an Epigenetic Drug on Development, Fecundity and Survivorship of Malaria Mosquitoes

Published on: January 16, 2015

Related Concept Videos

Pleiotropy01:33

Pleiotropy

Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
Inheritance of Chromatin Structures03:17

Inheritance of Chromatin Structures

Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying DNA...
Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
Chromatin Structure Regulates pre-mRNA Processing02:41

Chromatin Structure Regulates pre-mRNA Processing

In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...