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Differences of phosphoproteome between c-MYC and L-MYC during cellular reprogramming

ABSTRACT: MYC proteins (c-MYC, n-MYC, and L-MYC) are essential for improving reprogramming efficiency. L-MYC can generate iPSC colonies more efficiently than c-MYC. Still, it remains unknown what is the functional differences between c-MYC and L-MYC during cellular reprogramming. In this study, we performed proteome analysis to tackle this question and found MYC Box 0 (MB0) and 2 (MB2), one of the functional domains conserved in MYC family protein, might cause the phenotypic differences between the MYC proteins.

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Mio Iwasaki

PROVIDER: PXD027078 | JPOST Repository | Sat Jan 08 00:00:00 GMT 2022

REPOSITORIES: jPOST

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MYCL promotes iPSC-like colony formation via MYC Box 0 and 2 domains.

Akifuji Chiaki C Iwasaki Mio M Kawahara Yuka Y Sakurai Chiho C Cheng Yu-Shen YS Imai Takahiko T Nakagawa Masato M

Scientific reports 20211220 1

Human induced pluripotent stem cells (hiPSCs) can differentiate into cells of the three germ layers and are promising cell sources for regenerative medicine therapies. However, current protocols generate hiPSCs with low efficiency, and the generated iPSCs have variable differentiation capacity among different clones. Our previous study reported that MYC proteins (c-MYC and MYCL) are essential for reprogramming and germline transmission but that MYCL can generate hiPSC colonies more efficiently t ...[more]

PMID: 34930932

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Differences of proteome between c-MYC and L-MYC during cellular reprogramming

Project description:MYC proteins (c-MYC, n-MYC, and L-MYC) are essential for improving reprogramming efficiency. L-MYC can generate iPSC colonies more efficiently than c-MYC. Still, it remains unknown what is the functional differences between c-MYC and L-MYC during cellular reprogramming. In this study, we performed proteome analysis to tackle this question and found MYC Box 0 (MB0) and 2 (MB2), one of the functional domains conserved in MYC family protein, might cause the phenotypic differences between the MYC proteins.

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Project description:Embryonic stem cells are maintained in a self-renewing and pluripotent state by multiple regulatory pathways. Pluripotent-specific transcriptional networks are sequentially reactivated as somatic cells reprogram to achieve pluripotency. How epigenetic regulators modulate this process and contribute to somatic cell reprogramming is not clear. Here we perform a functional RNAi screen to identify the earliest epigenetic regulators required for reprogramming. We identify components of the SAGA histone acetyltransferase complex, in particular Gcn5, as critical regulators of reprogramming initiation. Furthermore, we show in mouse pluripotent stem cells that Gcn5 strongly associates with Myc and that upon initiation of somatic reprogramming, Gcn5 and Myc form a positive feed forward loop that activates a distinct alternative splicing network and the early acquisition of pluripotency-associated splicing events. These studies expose a Myc-SAGA pathway that drives expression of an essential alternative splicing regulatory network during somatic cell reprogramming. Examination of Myc-chromatin interactions in reprogramming cells

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