Dataset Information

ZSWIM4 regulates early embryonic patterning and BMP signaling pathway by promoting nuclear Smad1 degradation

ABSTRACT: The dorsoventral gradient of BMP signaling plays an essential role in embryonic patterning, with high BMP signal activating ventral-lateral mesoderm markers directly, and low BMP signal inducing neural tissues. The Zinc finger SWIM domain-containing protein 4 (zswim4) is expressed in the dorsal blastopore lip at the onset of Xenopus gastrula and then enriched at the forming neuroectoderm at mid-gastrula stages. Overexpression of zswim4 in Xenopus embryos causes inhibition of the anterior axis and shortened, curved body, and knockdown or knockout of zswim4 disturbed embryonic body axis formation and head development. The expression of ventral-lateral mesoderm marker genes was reduced after zswim4 overexpression and increased in embryos with zswim4 knockdown. Neural marker genes were repressed in zswim4 morphant. Mechanistically Zswim4 attenuates BMP signal through reducing protein stability of Smad1 in both Xenopus embryos and HEK293T cells. Zswim4 interacts with Smad1 and promotes ubiquitination of Smad1 in HEK293T cells. To identify the interaction partner of Zswim4 in regulating Smad1 stability, we performed SILAC based IP in HEK293T cells, and the precipitates were analyzed by Mass Spectrometry.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Yuanliang Zhang

LAB HEAD: Hui Zhao

PROVIDER: PXD035207 | Pride | 2024-05-22

REPOSITORIES: pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	20220430_forward_Z4_flag.raw	Raw
	20220430_forward_Z4_igg.raw	Raw
	20220430_forward_Z4_input.raw	Raw
	20220430_forward_Z6_flag.raw	Raw
	20220430_forward_Z6_igg.raw	Raw

Items per page:

1 - 5 of 17

Publications

ZSWIM4 regulates embryonic patterning and BMP signaling by promoting nuclear Smad1 degradation.

Wang Chengdong C Liu Ziran Z Zeng Yelin Y Zhou Liangji L Long Qi Q Hassan Imtiaz Ul IU Zhang Yuanliang Y Qi Xufeng X Cai Dongqing D Mao Bingyu B Lu Gang G Sun Jianmin J Yao Yonggang Y Deng Yi Y Zhao Qian Q Feng Bo B Zhou Qin Q Chan Wai Yee WY Zhao Hui H

EMBO reports 20240102 2

The dorsoventral gradient of BMP signaling plays an essential role in embryonic patterning. Zinc Finger SWIM-Type Containing 4 (zswim4) is expressed in the Spemann-Mangold organizer at the onset of Xenopus gastrulation and is then enriched in the developing neuroectoderm at the mid-gastrula stages. Knockdown or knockout of zswim4 causes ventralization. Overexpression of zswim4 decreases, whereas knockdown of zswim4 increases the expression levels of ventrolateral mesoderm marker genes. Mechanist ...[more]

PMID: 38177922

Similar Datasets

Project description:The motor neuron (MN)–hexamer complex consisting of LIM homeobox 3, Islet-1, and nuclear LIM interactor is a key determinant of motor neuron specification and differentiation. To gain insights into the transcriptional network in motor neuron development, we performed a genome-wide ChIP-sequencing analysis and found that the MN–hexamer directly regulates a wide array of motor neuron genes by binding to the HxRE (hexamer response element) shared among the target genes. Interestingly, STAT3-binding motif is highly enriched in the MN–hexamer–bound peaks in addition to the HxRE. We also found that a transcriptionally active form of STAT3 is expressed in embryonic motor neurons and that STAT3 associates with the MN–hexamer, enhancing the transcriptional activity of the MN–hexamer in an upstream signal-dependent manner. Correspondingly, STAT3 was needed for motor neuron differentiation in the developing spinal cord. Together, our studies uncover crucial gene regulatory mechanisms that couple MN–hexamer and STAT-activating extracellular signals to promote motor neuron differentiation in vertebrate spinal cord. To explain our experimental scheme briefly, we are interested in finding target sites for the dimer of transcription factors Isl1 and Lhx3. To mimic the biological activity of Isl1/Lhx3 dimer, we made Isl1-Lhx3 fusion and found that Isl1-Lhx3 has a potent biological activity in multiple systems (i.e. generation of ectopic motor neurons). Then we made ES cell line that induces Flag-tagged Isl1-Lhx3 expression upon Dox treatment. These *mouse* ES cells differentiate to motor neurons (iMN-ESCs) when treated with Dox following EB formation. To identify genomic binding sites of Isl1-Lhx3 (Flag-tagged), we performed ChIP with Flag antibody (pull down of Flag-Isl1-Lhx3) in ES cells treated with Dox. ChIP with Flag antibody in ES cells treated with vehicle (no Dox) was done as a negative control in parallel, and sequenced along with +Dox sample. We have done these experiments twice (two sets).