Identity-Seeking Self-Supervised Representation Learning for Generalizable Person Re-identification

This paper aims to learn a domain-generalizable (DG) person re-identification (ReID) representation from large-scale videos \textbf{without any annotation}. Prior DG ReID methods employ limited labeled data for training due to the high cost of annotation, which restricts further advances. To overcome the barriers of data and annotation, we propose to utilize large-scale unsupervised data for training. The key issue lies in how to mine identity information. To this end, we propose an Identity-seeking Self-supervised Representation learning (ISR) method. ISR constructs positive pairs from inter-frame images by modeling the instance association as a maximum-weight bipartite matching problem. A reliability-guided contrastive loss is further presented to suppress the adverse impact of noisy positive pairs, ensuring that reliable positive pairs dominate the learning process. The training cost of ISR scales approximately linearly with the data size, making it feasible to utilize large-scale data for training. The learned representation exhibits superior generalization ability. \textbf{Without human annotation and fine-tuning, ISR achieves 87.0\% Rank-1 on Market-1501 and 56.4\% Rank-1 on MSMT17}, outperforming the best supervised domain-generalizable method by 5.0\% and 19.5\%, respectively. In the pre-training$\rightarrow$fine-tuning scenario, ISR achieves state-of-the-art performance, with 88.4\% Rank-1 on MSMT17. The code is at \url{https://github.com/dcp15/ISR_ICCV2023_Oral}.Comment: ICCV 2023 Ora

Phosphorylation and an ATP-dependent process increase the dynamic exchange of H1 in chromatin

In Tetrahymena cells, phosphorylation of linker histone H1 regulates transcription of specific genes. Phosphorylation acts by creating a localized negative charge patch and phenocopies the loss of H1 from chromatin, suggesting that it affects transcription by regulating the dissociation of H1 from chromatin. To test this hypothesis, we used FRAP of GFP-tagged H1 to analyze the effects of mutations that either eliminate or mimic phosphorylation on the binding of H1 to chromatin both in vivo and in vitro. We demonstrate that phosphorylation can increase the rate of dissociation of H1 from chromatin, providing a mechanism by which it can affect H1 function in vivo. We also demonstrate a previously undescribed ATP-dependent process that has a global effect on the dynamic binding of linker histone to chromatin

Generalizable Re-Identification from Videos with Cycle Association

In this paper, we are interested in learning a generalizable person re-identification (re-ID) representation from unlabeled videos. Compared with 1) the popular unsupervised re-ID setting where the training and test sets are typically under the same domain, and 2) the popular domain generalization (DG) re-ID setting where the training samples are labeled, our novel scenario combines their key challenges: the training samples are unlabeled, and collected form various domains which do no align with the test domain. In other words, we aim to learn a representation in an unsupervised manner and directly use the learned representation for re-ID in novel domains. To fulfill this goal, we make two main contributions: First, we propose Cycle Association (CycAs), a scalable self-supervised learning method for re-ID with low training complexity; and second, we construct a large-scale unlabeled re-ID dataset named LMP-video, tailored for the proposed method. Specifically, CycAs learns re-ID features by enforcing cycle consistency of instance association between temporally successive video frame pairs, and the training cost is merely linear to the data size, making large-scale training possible. On the other hand, the LMP-video dataset is extremely large, containing 50 million unlabeled person images cropped from over 10K Youtube videos, therefore is sufficient to serve as fertile soil for self-supervised learning. Trained on LMP-video, we show that CycAs learns good generalization towards novel domains. The achieved results sometimes even outperform supervised domain generalizable models. Remarkably, CycAs achieves 82.2% Rank-1 on Market-1501 and 49.0% Rank-1 on MSMT17 with zero human annotation, surpassing state-of-the-art supervised DG re-ID methods. Moreover, we also demonstrate the superiority of CycAs under the canonical unsupervised re-ID and the pretrain-and-finetune scenarios

NSUN2‐Mediated m5C Methylation and METTL3/METTL14‐Mediated m6A Methylation Cooperatively Enhance p21 Translation

N6‐methyladenosine (m6A) and m5C methylation are two major types of RNA methylation, but the impact of joint modifications on the same mRNA is unknown. Here, we show that in p21 3′UTR, NSUN2 catalyzes m5C modification and METTL3/METTL14 catalyzes m6A modification. Interestingly, methylation at m6A by METTL3/METTL14 facilitates the methylation of m5C by NSUN2, and vice versa. NSUN2‐mediated m5C and METTL3/METTL14‐mediated m6A methylation synergistically enhance p21 expression at the translational level, leading to elevated expression of p21 in oxidative stress‐induced cellular senescence. Our findings on p21 mRNA methylation and expression reveal that joint m6A and m5C modification of the same RNA may influence each other, coordinately affecting protein expression patterns. J. Cell. Biochem. 118: 2587–2598, 2017. © 2017 Wiley Periodicals, Inc.In p21 3’UTR,NSUN2 catalyzes m5C modification and METTL3/METTL14 catalyzes m6A modification. Methylation at m6A by METTL3/METTL14 facilitates the methylation of m5C by NSUN2, and vice versa. NSUN2‐mediated m5C and METTL3/METTL14‐mediated m6A methylation synergistically enhance p21 expression at the translational level, leading to elevated expression of p21 in oxidative stress‐induced cellular senescence.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137760/1/jcb25957.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137760/2/jcb25957_am.pd

The Histone Acetyltransferase MOF Is a Key Regulator of the Embryonic Stem Cell Core Transcriptional Network

SummaryPluripotent embryonic stem cells (ESCs) maintain self-renewal and the potential for rapid response to differentiation cues. Both ESC features are subject to epigenetic regulation. Here we show that the histone acetyltransferase Mof plays an essential role in the maintenance of ESC self-renewal and pluripotency. ESCs with Mof deletion lose characteristic morphology, alkaline phosphatase (AP) staining, and differentiation potential. They also have aberrant expression of the core transcription factors Nanog, Oct4, and Sox2. Importantly, the phenotypes of Mof null ESCs can be partially suppressed by Nanog overexpression, supporting the idea that Mof functions as an upstream regulator of Nanog in ESCs. Genome-wide ChIP-sequencing and transcriptome analyses further demonstrate that Mof is an integral component of the ESC core transcriptional network and that Mof primes genes for diverse developmental programs. Mof is also required for Wdr5 recruitment and H3K4 methylation at key regulatory loci, highlighting the complexity and interconnectivity of various chromatin regulators in ESCs

An Ash2L/RbBP5 Heterodimer Stimulates the MLL1 Methyltransferase Activity through Coordinated Substrate Interactions with the MLL1 SET Domain

Histone H3 lysine 4 (K4) methylation is a prevalent mark associated with transcription activation and is mainly catalyzed by the MLL/SET1 family histone methyltransferases. A common feature of the mammalian MLL/SET1 complexes is the presence of three core components (RbBP5, Ash2L and WDR5) and a catalytic subunit containing a SET domain. Unlike most other histone lysine methyltransferases, all four proteins are required for efficient H3 K4 methylation. Despite extensive efforts, mechanisms for how three core components regulate MLL/SET1 methyltransferase activity remain elusive. Here we show that a heterodimer of Ash2L and RbBP5 has intrinsic histone methyltransferase activity. This activity requires the highly conserved SPRY domain of Ash2L and a short peptide of RbBP5. We demonstrate that both Ash2L and the MLL1 SET domain are capable of binding to S-adenosyl-L- [methyl-3H] methionine in the MLL1 core complex. Mutations in the MLL1 SET domain that fail to support overall H3 K4 methylation also compromise SAM binding by Ash2L. Taken together, our results show that the Ash2L/RbBP5 heterodimer plays a critical role in the overall catalysis of MLL1 mediated H3 K4 methylation. The results we describe here provide mechanistic insights for unique regulation of the MLL1 methyltransferase activity. It suggests that both Ash2L/RbBP5 and the MLL1 SET domain make direct contacts with the substrates and contribute to the formation of a joint catalytic center. Given the shared core configuration among all MLL/SET1 family HMTs, it will be interesting to test whether the mechanism we describe here can be generalized to other MLL/SET1 family members in the future

Impaired CD4 + T-cell proliferation and effector function correlates with repressive histone methylation events in a mouse model of severe sepsis

Immunosuppression following severe sepsis remains a significant human health concern, as long-term morbidity and mortality rates of patients who have recovered from life-threatening septic shock remain poor. Mouse models of severe sepsis indicate this immunosuppression may be partly due to alterations in myeloid cell function; however, the effect of severe sepsis on subsequent CD4 + T-cell responses remains unclear. In the present study, CD4 + T cells from mice subjected to an experimental model of severe sepsis (cecal ligation and puncture (CLP)) were analyzed in vitro . CD4 + CD62L + T cells from CLP mice exhibited reduced proliferative capacity and altered gene expression. Additionally, CD4 + CD62L + T cells from CLP mice exhibit dysregulated cytokine production after in vitro skewing with exogenous cytokines, indicating a decreased capability of these cells to commit to either the T H 1 or T H 2 lineage. Repressive histone methylation marks were also evident at promoter regions for the T H 1 cytokine IFN-Γ and the T H 2 transcription factor GATA-3 in naÏve CD4 + T cells from CLP mice. These results provide evidence that CD4 + T-cell subsets from post-septic mice exhibit defects in activation and effector function, possibly due to chromatin remodeling proximal to genes involved in cytokine production or gene transcription.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71365/1/998_ftp.pd

Targeting Mll1 H3K4 methyltransferase activity to guide cardiac lineage specific reprogramming of fibroblasts

Generation of induced cardiomyocytes (iCMs) directly from fibroblasts offers a great opportunity for cardiac disease modeling and cardiac regeneration. A major challenge of iCM generation is the low conversion rate. To address this issue, we attempted to identify small molecules that could potentiate the reprogramming ability towards cardiac fate by removing inhibitory roadblocks. Using mouse embryonic fibroblasts as the starting cell source, we first screened 47 cardiac development related epigenetic and transcription factors, and identified an unexpected role of H3K4 methyltransferase Mll1 and related factor Men1 in inhibiting iCM reprogramming. We then applied small molecules (MM408 and MI503) of Mll1 pathway inhibitors and observed an improved efficiency in converting embryonic fibroblasts and cardiac fibroblasts into functional cardiomyocyte-like cells. We further observed that these inhibitors directly suppressed the expression of Mll1 target gene Ebf1 involved in adipocyte differentiation. Consequently, Mll1 inhibition significantly decreased the formation of adipocytes during iCM induction. Therefore, Mll1 inhibitors likely increased iCM efficiency by suppressing alternative lineage gene expression. Our studies show that targeting Mll1 dependent H3K4 methyltransferase activity provides specificity in the process of cardiac reprogramming. These findings shed new light on the molecular mechanisms underlying cardiac conversion of fibroblasts and provide novel targets and small molecules to improve iCM reprogramming for clinical applications

let‐7‐repressesed S hc translation delays replicative senescence

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102709/1/acel12176.pd